Systematic co-delivery of dual agonists to enhance cancer immunotherapy
Abstract In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8...
Ausführliche Beschreibung
Autor*in: |
Li, Xiangxia [verfasserIn] |
---|
Format: |
E-Artikel |
---|---|
Sprache: |
Englisch |
Erschienen: |
2022 |
---|
Schlagwörter: |
toll-like receptors (TLRs) agonists mesoporous silica nanoparticles (MSNs) |
---|
Anmerkung: |
© Tsinghua University Press 2022 |
---|
Übergeordnetes Werk: |
Enthalten in: Nano research - [S.l.] : Tsinghua Press, 2008, 15(2022), 9 vom: 20. Juni, Seite 8326-8335 |
---|---|
Übergeordnetes Werk: |
volume:15 ; year:2022 ; number:9 ; day:20 ; month:06 ; pages:8326-8335 |
Links: |
---|
DOI / URN: |
10.1007/s12274-022-4504-2 |
---|
Katalog-ID: |
SPR050931016 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | SPR050931016 | ||
003 | DE-627 | ||
005 | 20230509105955.0 | ||
007 | cr uuu---uuuuu | ||
008 | 230508s2022 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1007/s12274-022-4504-2 |2 doi | |
035 | |a (DE-627)SPR050931016 | ||
035 | |a (SPR)s12274-022-4504-2-e | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Li, Xiangxia |e verfasserin |4 aut | |
245 | 1 | 0 | |a Systematic co-delivery of dual agonists to enhance cancer immunotherapy |
264 | 1 | |c 2022 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
500 | |a © Tsinghua University Press 2022 | ||
520 | |a Abstract In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy. Here, we designed a lipid-coated mesoporous silica nanoparticle (MSNsLipo) for the co-delivery of TLR7/8 agonist resiquimod (R848) and TLR9 agonist CpG oligodeoxynucleotides (ODNs) (CpG@MSNs-R@L-M). R848 was firstly conjugated onto the nanoparticle via silane chemistry, which is acidic responsive drug release. Then, CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848. Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs. More importantly, CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model. The mechanistic study demonstrated that CpG@MSNs-R@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells. It was concluded that in comparison to single agonist, the co-delivery of dual agonists, CpG and R848, can improve anti-tumor immune responses for cancer immunotherapy. | ||
650 | 4 | |a toll-like receptors (TLRs) agonists |7 (dpeaa)DE-He213 | |
650 | 4 | |a mesoporous silica nanoparticles (MSNs) |7 (dpeaa)DE-He213 | |
650 | 4 | |a drug delivery |7 (dpeaa)DE-He213 | |
650 | 4 | |a tumor immunosuppressive microenvironment (TIME) |7 (dpeaa)DE-He213 | |
650 | 4 | |a cancer immunotherapy |7 (dpeaa)DE-He213 | |
700 | 1 | |a Chen, Guiyuan |4 aut | |
700 | 1 | |a Wang, Yangyi |4 aut | |
700 | 1 | |a Su, Lanhong |4 aut | |
700 | 1 | |a Chen, Bo |4 aut | |
700 | 1 | |a Wu, Kecheng |4 aut | |
700 | 1 | |a Xing, Yun |4 aut | |
700 | 1 | |a Song, Zechenxi |4 aut | |
700 | 1 | |a Dai, Ruike |4 aut | |
700 | 1 | |a Liu, Tianxin |4 aut | |
700 | 1 | |a Zhao, Jiaao |4 aut | |
700 | 1 | |a Xie, Zhe |4 aut | |
700 | 1 | |a Zhou, Peijie |4 aut | |
700 | 1 | |a Xia, Xiaoping |4 aut | |
700 | 1 | |a Min, Yuanzeng |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Nano research |d [S.l.] : Tsinghua Press, 2008 |g 15(2022), 9 vom: 20. Juni, Seite 8326-8335 |w (DE-627)57375361X |w (DE-600)2442216-2 |x 1998-0000 |7 nnns |
773 | 1 | 8 | |g volume:15 |g year:2022 |g number:9 |g day:20 |g month:06 |g pages:8326-8335 |
856 | 4 | 0 | |u https://dx.doi.org/10.1007/s12274-022-4504-2 |z lizenzpflichtig |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a SYSFLAG_A | ||
912 | |a GBV_SPRINGER | ||
912 | |a GBV_ILN_11 | ||
912 | |a GBV_ILN_20 | ||
912 | |a GBV_ILN_22 | ||
912 | |a GBV_ILN_23 | ||
912 | |a GBV_ILN_24 | ||
912 | |a GBV_ILN_31 | ||
912 | |a GBV_ILN_32 | ||
912 | |a GBV_ILN_39 | ||
912 | |a GBV_ILN_40 | ||
912 | |a GBV_ILN_60 | ||
912 | |a GBV_ILN_62 | ||
912 | |a GBV_ILN_63 | ||
912 | |a GBV_ILN_65 | ||
912 | |a GBV_ILN_69 | ||
912 | |a GBV_ILN_70 | ||
912 | |a GBV_ILN_73 | ||
912 | |a GBV_ILN_74 | ||
912 | |a GBV_ILN_90 | ||
912 | |a GBV_ILN_95 | ||
912 | |a GBV_ILN_100 | ||
912 | |a GBV_ILN_101 | ||
912 | |a GBV_ILN_105 | ||
912 | |a GBV_ILN_110 | ||
912 | |a GBV_ILN_120 | ||
912 | |a GBV_ILN_138 | ||
912 | |a GBV_ILN_150 | ||
912 | |a GBV_ILN_151 | ||
912 | |a GBV_ILN_152 | ||
912 | |a GBV_ILN_161 | ||
912 | |a GBV_ILN_170 | ||
912 | |a GBV_ILN_171 | ||
912 | |a GBV_ILN_187 | ||
912 | |a GBV_ILN_213 | ||
912 | |a GBV_ILN_224 | ||
912 | |a GBV_ILN_230 | ||
912 | |a GBV_ILN_250 | ||
912 | |a GBV_ILN_281 | ||
912 | |a GBV_ILN_285 | ||
912 | |a GBV_ILN_293 | ||
912 | |a GBV_ILN_370 | ||
912 | |a GBV_ILN_602 | ||
912 | |a GBV_ILN_636 | ||
912 | |a GBV_ILN_702 | ||
912 | |a GBV_ILN_2001 | ||
912 | |a GBV_ILN_2003 | ||
912 | |a GBV_ILN_2004 | ||
912 | |a GBV_ILN_2005 | ||
912 | |a GBV_ILN_2006 | ||
912 | |a GBV_ILN_2007 | ||
912 | |a GBV_ILN_2008 | ||
912 | |a GBV_ILN_2009 | ||
912 | |a GBV_ILN_2010 | ||
912 | |a GBV_ILN_2011 | ||
912 | |a GBV_ILN_2014 | ||
912 | |a GBV_ILN_2015 | ||
912 | |a GBV_ILN_2020 | ||
912 | |a GBV_ILN_2021 | ||
912 | |a GBV_ILN_2025 | ||
912 | |a GBV_ILN_2026 | ||
912 | |a GBV_ILN_2027 | ||
912 | |a GBV_ILN_2031 | ||
912 | |a GBV_ILN_2034 | ||
912 | |a GBV_ILN_2037 | ||
912 | |a GBV_ILN_2038 | ||
912 | |a GBV_ILN_2039 | ||
912 | |a GBV_ILN_2044 | ||
912 | |a GBV_ILN_2048 | ||
912 | |a GBV_ILN_2049 | ||
912 | |a GBV_ILN_2050 | ||
912 | |a GBV_ILN_2055 | ||
912 | |a GBV_ILN_2056 | ||
912 | |a GBV_ILN_2057 | ||
912 | |a GBV_ILN_2059 | ||
912 | |a GBV_ILN_2061 | ||
912 | |a GBV_ILN_2064 | ||
912 | |a GBV_ILN_2065 | ||
912 | |a GBV_ILN_2068 | ||
912 | |a GBV_ILN_2088 | ||
912 | |a GBV_ILN_2093 | ||
912 | |a GBV_ILN_2106 | ||
912 | |a GBV_ILN_2107 | ||
912 | |a GBV_ILN_2108 | ||
912 | |a GBV_ILN_2110 | ||
912 | |a GBV_ILN_2111 | ||
912 | |a GBV_ILN_2112 | ||
912 | |a GBV_ILN_2113 | ||
912 | |a GBV_ILN_2118 | ||
912 | |a GBV_ILN_2122 | ||
912 | |a GBV_ILN_2129 | ||
912 | |a GBV_ILN_2143 | ||
912 | |a GBV_ILN_2144 | ||
912 | |a GBV_ILN_2147 | ||
912 | |a GBV_ILN_2148 | ||
912 | |a GBV_ILN_2152 | ||
912 | |a GBV_ILN_2153 | ||
912 | |a GBV_ILN_2188 | ||
912 | |a GBV_ILN_2190 | ||
912 | |a GBV_ILN_2232 | ||
912 | |a GBV_ILN_2336 | ||
912 | |a GBV_ILN_2446 | ||
912 | |a GBV_ILN_2470 | ||
912 | |a GBV_ILN_2472 | ||
912 | |a GBV_ILN_2507 | ||
912 | |a GBV_ILN_2522 | ||
912 | |a GBV_ILN_2548 | ||
912 | |a GBV_ILN_4035 | ||
912 | |a GBV_ILN_4037 | ||
912 | |a GBV_ILN_4046 | ||
912 | |a GBV_ILN_4112 | ||
912 | |a GBV_ILN_4125 | ||
912 | |a GBV_ILN_4126 | ||
912 | |a GBV_ILN_4242 | ||
912 | |a GBV_ILN_4246 | ||
912 | |a GBV_ILN_4249 | ||
912 | |a GBV_ILN_4251 | ||
912 | |a GBV_ILN_4305 | ||
912 | |a GBV_ILN_4306 | ||
912 | |a GBV_ILN_4307 | ||
912 | |a GBV_ILN_4313 | ||
912 | |a GBV_ILN_4322 | ||
912 | |a GBV_ILN_4323 | ||
912 | |a GBV_ILN_4324 | ||
912 | |a GBV_ILN_4325 | ||
912 | |a GBV_ILN_4326 | ||
912 | |a GBV_ILN_4328 | ||
912 | |a GBV_ILN_4333 | ||
912 | |a GBV_ILN_4334 | ||
912 | |a GBV_ILN_4335 | ||
912 | |a GBV_ILN_4336 | ||
912 | |a GBV_ILN_4338 | ||
912 | |a GBV_ILN_4393 | ||
912 | |a GBV_ILN_4700 | ||
951 | |a AR | ||
952 | |d 15 |j 2022 |e 9 |b 20 |c 06 |h 8326-8335 |
author_variant |
x l xl g c gc y w yw l s ls b c bc k w kw y x yx z s zs r d rd t l tl j z jz z x zx p z pz x x xx y m ym |
---|---|
matchkey_str |
article:19980000:2022----::ytmtcoeieyfulgnssonacc |
hierarchy_sort_str |
2022 |
publishDate |
2022 |
allfields |
10.1007/s12274-022-4504-2 doi (DE-627)SPR050931016 (SPR)s12274-022-4504-2-e DE-627 ger DE-627 rakwb eng Li, Xiangxia verfasserin aut Systematic co-delivery of dual agonists to enhance cancer immunotherapy 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Tsinghua University Press 2022 Abstract In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy. Here, we designed a lipid-coated mesoporous silica nanoparticle (MSNsLipo) for the co-delivery of TLR7/8 agonist resiquimod (R848) and TLR9 agonist CpG oligodeoxynucleotides (ODNs) (CpG@MSNs-R@L-M). R848 was firstly conjugated onto the nanoparticle via silane chemistry, which is acidic responsive drug release. Then, CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848. Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs. More importantly, CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model. The mechanistic study demonstrated that CpG@MSNs-R@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells. It was concluded that in comparison to single agonist, the co-delivery of dual agonists, CpG and R848, can improve anti-tumor immune responses for cancer immunotherapy. toll-like receptors (TLRs) agonists (dpeaa)DE-He213 mesoporous silica nanoparticles (MSNs) (dpeaa)DE-He213 drug delivery (dpeaa)DE-He213 tumor immunosuppressive microenvironment (TIME) (dpeaa)DE-He213 cancer immunotherapy (dpeaa)DE-He213 Chen, Guiyuan aut Wang, Yangyi aut Su, Lanhong aut Chen, Bo aut Wu, Kecheng aut Xing, Yun aut Song, Zechenxi aut Dai, Ruike aut Liu, Tianxin aut Zhao, Jiaao aut Xie, Zhe aut Zhou, Peijie aut Xia, Xiaoping aut Min, Yuanzeng aut Enthalten in Nano research [S.l.] : Tsinghua Press, 2008 15(2022), 9 vom: 20. Juni, Seite 8326-8335 (DE-627)57375361X (DE-600)2442216-2 1998-0000 nnns volume:15 year:2022 number:9 day:20 month:06 pages:8326-8335 https://dx.doi.org/10.1007/s12274-022-4504-2 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 15 2022 9 20 06 8326-8335 |
spelling |
10.1007/s12274-022-4504-2 doi (DE-627)SPR050931016 (SPR)s12274-022-4504-2-e DE-627 ger DE-627 rakwb eng Li, Xiangxia verfasserin aut Systematic co-delivery of dual agonists to enhance cancer immunotherapy 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Tsinghua University Press 2022 Abstract In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy. Here, we designed a lipid-coated mesoporous silica nanoparticle (MSNsLipo) for the co-delivery of TLR7/8 agonist resiquimod (R848) and TLR9 agonist CpG oligodeoxynucleotides (ODNs) (CpG@MSNs-R@L-M). R848 was firstly conjugated onto the nanoparticle via silane chemistry, which is acidic responsive drug release. Then, CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848. Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs. More importantly, CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model. The mechanistic study demonstrated that CpG@MSNs-R@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells. It was concluded that in comparison to single agonist, the co-delivery of dual agonists, CpG and R848, can improve anti-tumor immune responses for cancer immunotherapy. toll-like receptors (TLRs) agonists (dpeaa)DE-He213 mesoporous silica nanoparticles (MSNs) (dpeaa)DE-He213 drug delivery (dpeaa)DE-He213 tumor immunosuppressive microenvironment (TIME) (dpeaa)DE-He213 cancer immunotherapy (dpeaa)DE-He213 Chen, Guiyuan aut Wang, Yangyi aut Su, Lanhong aut Chen, Bo aut Wu, Kecheng aut Xing, Yun aut Song, Zechenxi aut Dai, Ruike aut Liu, Tianxin aut Zhao, Jiaao aut Xie, Zhe aut Zhou, Peijie aut Xia, Xiaoping aut Min, Yuanzeng aut Enthalten in Nano research [S.l.] : Tsinghua Press, 2008 15(2022), 9 vom: 20. Juni, Seite 8326-8335 (DE-627)57375361X (DE-600)2442216-2 1998-0000 nnns volume:15 year:2022 number:9 day:20 month:06 pages:8326-8335 https://dx.doi.org/10.1007/s12274-022-4504-2 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 15 2022 9 20 06 8326-8335 |
allfields_unstemmed |
10.1007/s12274-022-4504-2 doi (DE-627)SPR050931016 (SPR)s12274-022-4504-2-e DE-627 ger DE-627 rakwb eng Li, Xiangxia verfasserin aut Systematic co-delivery of dual agonists to enhance cancer immunotherapy 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Tsinghua University Press 2022 Abstract In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy. Here, we designed a lipid-coated mesoporous silica nanoparticle (MSNsLipo) for the co-delivery of TLR7/8 agonist resiquimod (R848) and TLR9 agonist CpG oligodeoxynucleotides (ODNs) (CpG@MSNs-R@L-M). R848 was firstly conjugated onto the nanoparticle via silane chemistry, which is acidic responsive drug release. Then, CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848. Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs. More importantly, CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model. The mechanistic study demonstrated that CpG@MSNs-R@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells. It was concluded that in comparison to single agonist, the co-delivery of dual agonists, CpG and R848, can improve anti-tumor immune responses for cancer immunotherapy. toll-like receptors (TLRs) agonists (dpeaa)DE-He213 mesoporous silica nanoparticles (MSNs) (dpeaa)DE-He213 drug delivery (dpeaa)DE-He213 tumor immunosuppressive microenvironment (TIME) (dpeaa)DE-He213 cancer immunotherapy (dpeaa)DE-He213 Chen, Guiyuan aut Wang, Yangyi aut Su, Lanhong aut Chen, Bo aut Wu, Kecheng aut Xing, Yun aut Song, Zechenxi aut Dai, Ruike aut Liu, Tianxin aut Zhao, Jiaao aut Xie, Zhe aut Zhou, Peijie aut Xia, Xiaoping aut Min, Yuanzeng aut Enthalten in Nano research [S.l.] : Tsinghua Press, 2008 15(2022), 9 vom: 20. Juni, Seite 8326-8335 (DE-627)57375361X (DE-600)2442216-2 1998-0000 nnns volume:15 year:2022 number:9 day:20 month:06 pages:8326-8335 https://dx.doi.org/10.1007/s12274-022-4504-2 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 15 2022 9 20 06 8326-8335 |
allfieldsGer |
10.1007/s12274-022-4504-2 doi (DE-627)SPR050931016 (SPR)s12274-022-4504-2-e DE-627 ger DE-627 rakwb eng Li, Xiangxia verfasserin aut Systematic co-delivery of dual agonists to enhance cancer immunotherapy 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Tsinghua University Press 2022 Abstract In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy. Here, we designed a lipid-coated mesoporous silica nanoparticle (MSNsLipo) for the co-delivery of TLR7/8 agonist resiquimod (R848) and TLR9 agonist CpG oligodeoxynucleotides (ODNs) (CpG@MSNs-R@L-M). R848 was firstly conjugated onto the nanoparticle via silane chemistry, which is acidic responsive drug release. Then, CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848. Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs. More importantly, CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model. The mechanistic study demonstrated that CpG@MSNs-R@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells. It was concluded that in comparison to single agonist, the co-delivery of dual agonists, CpG and R848, can improve anti-tumor immune responses for cancer immunotherapy. toll-like receptors (TLRs) agonists (dpeaa)DE-He213 mesoporous silica nanoparticles (MSNs) (dpeaa)DE-He213 drug delivery (dpeaa)DE-He213 tumor immunosuppressive microenvironment (TIME) (dpeaa)DE-He213 cancer immunotherapy (dpeaa)DE-He213 Chen, Guiyuan aut Wang, Yangyi aut Su, Lanhong aut Chen, Bo aut Wu, Kecheng aut Xing, Yun aut Song, Zechenxi aut Dai, Ruike aut Liu, Tianxin aut Zhao, Jiaao aut Xie, Zhe aut Zhou, Peijie aut Xia, Xiaoping aut Min, Yuanzeng aut Enthalten in Nano research [S.l.] : Tsinghua Press, 2008 15(2022), 9 vom: 20. Juni, Seite 8326-8335 (DE-627)57375361X (DE-600)2442216-2 1998-0000 nnns volume:15 year:2022 number:9 day:20 month:06 pages:8326-8335 https://dx.doi.org/10.1007/s12274-022-4504-2 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 15 2022 9 20 06 8326-8335 |
allfieldsSound |
10.1007/s12274-022-4504-2 doi (DE-627)SPR050931016 (SPR)s12274-022-4504-2-e DE-627 ger DE-627 rakwb eng Li, Xiangxia verfasserin aut Systematic co-delivery of dual agonists to enhance cancer immunotherapy 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Tsinghua University Press 2022 Abstract In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy. Here, we designed a lipid-coated mesoporous silica nanoparticle (MSNsLipo) for the co-delivery of TLR7/8 agonist resiquimod (R848) and TLR9 agonist CpG oligodeoxynucleotides (ODNs) (CpG@MSNs-R@L-M). R848 was firstly conjugated onto the nanoparticle via silane chemistry, which is acidic responsive drug release. Then, CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848. Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs. More importantly, CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model. The mechanistic study demonstrated that CpG@MSNs-R@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells. It was concluded that in comparison to single agonist, the co-delivery of dual agonists, CpG and R848, can improve anti-tumor immune responses for cancer immunotherapy. toll-like receptors (TLRs) agonists (dpeaa)DE-He213 mesoporous silica nanoparticles (MSNs) (dpeaa)DE-He213 drug delivery (dpeaa)DE-He213 tumor immunosuppressive microenvironment (TIME) (dpeaa)DE-He213 cancer immunotherapy (dpeaa)DE-He213 Chen, Guiyuan aut Wang, Yangyi aut Su, Lanhong aut Chen, Bo aut Wu, Kecheng aut Xing, Yun aut Song, Zechenxi aut Dai, Ruike aut Liu, Tianxin aut Zhao, Jiaao aut Xie, Zhe aut Zhou, Peijie aut Xia, Xiaoping aut Min, Yuanzeng aut Enthalten in Nano research [S.l.] : Tsinghua Press, 2008 15(2022), 9 vom: 20. Juni, Seite 8326-8335 (DE-627)57375361X (DE-600)2442216-2 1998-0000 nnns volume:15 year:2022 number:9 day:20 month:06 pages:8326-8335 https://dx.doi.org/10.1007/s12274-022-4504-2 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 15 2022 9 20 06 8326-8335 |
language |
English |
source |
Enthalten in Nano research 15(2022), 9 vom: 20. Juni, Seite 8326-8335 volume:15 year:2022 number:9 day:20 month:06 pages:8326-8335 |
sourceStr |
Enthalten in Nano research 15(2022), 9 vom: 20. Juni, Seite 8326-8335 volume:15 year:2022 number:9 day:20 month:06 pages:8326-8335 |
format_phy_str_mv |
Article |
institution |
findex.gbv.de |
topic_facet |
toll-like receptors (TLRs) agonists mesoporous silica nanoparticles (MSNs) drug delivery tumor immunosuppressive microenvironment (TIME) cancer immunotherapy |
isfreeaccess_bool |
false |
container_title |
Nano research |
authorswithroles_txt_mv |
Li, Xiangxia @@aut@@ Chen, Guiyuan @@aut@@ Wang, Yangyi @@aut@@ Su, Lanhong @@aut@@ Chen, Bo @@aut@@ Wu, Kecheng @@aut@@ Xing, Yun @@aut@@ Song, Zechenxi @@aut@@ Dai, Ruike @@aut@@ Liu, Tianxin @@aut@@ Zhao, Jiaao @@aut@@ Xie, Zhe @@aut@@ Zhou, Peijie @@aut@@ Xia, Xiaoping @@aut@@ Min, Yuanzeng @@aut@@ |
publishDateDaySort_date |
2022-06-20T00:00:00Z |
hierarchy_top_id |
57375361X |
id |
SPR050931016 |
language_de |
englisch |
fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR050931016</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230509105955.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230508s2022 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s12274-022-4504-2</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR050931016</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s12274-022-4504-2-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Li, Xiangxia</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Systematic co-delivery of dual agonists to enhance cancer immunotherapy</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2022</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© Tsinghua University Press 2022</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy. Here, we designed a lipid-coated mesoporous silica nanoparticle (MSNsLipo) for the co-delivery of TLR7/8 agonist resiquimod (R848) and TLR9 agonist CpG oligodeoxynucleotides (ODNs) (CpG@MSNs-R@L-M). R848 was firstly conjugated onto the nanoparticle via silane chemistry, which is acidic responsive drug release. Then, CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848. Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs. More importantly, CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model. The mechanistic study demonstrated that CpG@MSNs-R@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells. It was concluded that in comparison to single agonist, the co-delivery of dual agonists, CpG and R848, can improve anti-tumor immune responses for cancer immunotherapy.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">toll-like receptors (TLRs) agonists</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">mesoporous silica nanoparticles (MSNs)</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">drug delivery</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">tumor immunosuppressive microenvironment (TIME)</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">cancer immunotherapy</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Chen, Guiyuan</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wang, Yangyi</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Su, Lanhong</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Chen, Bo</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wu, Kecheng</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Xing, Yun</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Song, Zechenxi</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dai, Ruike</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Liu, Tianxin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhao, Jiaao</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Xie, Zhe</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhou, Peijie</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Xia, Xiaoping</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Min, Yuanzeng</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Nano research</subfield><subfield code="d">[S.l.] : Tsinghua Press, 2008</subfield><subfield code="g">15(2022), 9 vom: 20. Juni, Seite 8326-8335</subfield><subfield code="w">(DE-627)57375361X</subfield><subfield code="w">(DE-600)2442216-2</subfield><subfield code="x">1998-0000</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:15</subfield><subfield code="g">year:2022</subfield><subfield code="g">number:9</subfield><subfield code="g">day:20</subfield><subfield code="g">month:06</subfield><subfield code="g">pages:8326-8335</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1007/s12274-022-4504-2</subfield><subfield code="z">lizenzpflichtig</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_32</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_90</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_100</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_101</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_120</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_138</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_150</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_152</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_171</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_187</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_224</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_250</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_281</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_370</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_636</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_702</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2001</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2004</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2006</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2007</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2008</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2010</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2011</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2015</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2020</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2021</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2025</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2026</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2027</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2031</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2034</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2038</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2039</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2044</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2048</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2049</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2050</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2056</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2057</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2059</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2061</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2064</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2065</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2068</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2088</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2093</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2106</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2107</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2108</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2113</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2118</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2122</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2129</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2143</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2144</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2147</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2148</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2152</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2153</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2188</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2190</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2232</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2336</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2446</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2470</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2472</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2507</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2522</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2548</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4035</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4046</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4242</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4246</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4251</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4326</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4328</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4333</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4334</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4335</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4336</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4393</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">15</subfield><subfield code="j">2022</subfield><subfield code="e">9</subfield><subfield code="b">20</subfield><subfield code="c">06</subfield><subfield code="h">8326-8335</subfield></datafield></record></collection>
|
author |
Li, Xiangxia |
spellingShingle |
Li, Xiangxia misc toll-like receptors (TLRs) agonists misc mesoporous silica nanoparticles (MSNs) misc drug delivery misc tumor immunosuppressive microenvironment (TIME) misc cancer immunotherapy Systematic co-delivery of dual agonists to enhance cancer immunotherapy |
authorStr |
Li, Xiangxia |
ppnlink_with_tag_str_mv |
@@773@@(DE-627)57375361X |
format |
electronic Article |
delete_txt_mv |
keep |
author_role |
aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut |
collection |
springer |
remote_str |
true |
illustrated |
Not Illustrated |
issn |
1998-0000 |
topic_title |
Systematic co-delivery of dual agonists to enhance cancer immunotherapy toll-like receptors (TLRs) agonists (dpeaa)DE-He213 mesoporous silica nanoparticles (MSNs) (dpeaa)DE-He213 drug delivery (dpeaa)DE-He213 tumor immunosuppressive microenvironment (TIME) (dpeaa)DE-He213 cancer immunotherapy (dpeaa)DE-He213 |
topic |
misc toll-like receptors (TLRs) agonists misc mesoporous silica nanoparticles (MSNs) misc drug delivery misc tumor immunosuppressive microenvironment (TIME) misc cancer immunotherapy |
topic_unstemmed |
misc toll-like receptors (TLRs) agonists misc mesoporous silica nanoparticles (MSNs) misc drug delivery misc tumor immunosuppressive microenvironment (TIME) misc cancer immunotherapy |
topic_browse |
misc toll-like receptors (TLRs) agonists misc mesoporous silica nanoparticles (MSNs) misc drug delivery misc tumor immunosuppressive microenvironment (TIME) misc cancer immunotherapy |
format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
format_main_str_mv |
Text Zeitschrift/Artikel |
carriertype_str_mv |
cr |
hierarchy_parent_title |
Nano research |
hierarchy_parent_id |
57375361X |
hierarchy_top_title |
Nano research |
isfreeaccess_txt |
false |
familylinks_str_mv |
(DE-627)57375361X (DE-600)2442216-2 |
title |
Systematic co-delivery of dual agonists to enhance cancer immunotherapy |
ctrlnum |
(DE-627)SPR050931016 (SPR)s12274-022-4504-2-e |
title_full |
Systematic co-delivery of dual agonists to enhance cancer immunotherapy |
author_sort |
Li, Xiangxia |
journal |
Nano research |
journalStr |
Nano research |
lang_code |
eng |
isOA_bool |
false |
recordtype |
marc |
publishDateSort |
2022 |
contenttype_str_mv |
txt |
container_start_page |
8326 |
author_browse |
Li, Xiangxia Chen, Guiyuan Wang, Yangyi Su, Lanhong Chen, Bo Wu, Kecheng Xing, Yun Song, Zechenxi Dai, Ruike Liu, Tianxin Zhao, Jiaao Xie, Zhe Zhou, Peijie Xia, Xiaoping Min, Yuanzeng |
container_volume |
15 |
format_se |
Elektronische Aufsätze |
author-letter |
Li, Xiangxia |
doi_str_mv |
10.1007/s12274-022-4504-2 |
title_sort |
systematic co-delivery of dual agonists to enhance cancer immunotherapy |
title_auth |
Systematic co-delivery of dual agonists to enhance cancer immunotherapy |
abstract |
Abstract In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy. Here, we designed a lipid-coated mesoporous silica nanoparticle (MSNsLipo) for the co-delivery of TLR7/8 agonist resiquimod (R848) and TLR9 agonist CpG oligodeoxynucleotides (ODNs) (CpG@MSNs-R@L-M). R848 was firstly conjugated onto the nanoparticle via silane chemistry, which is acidic responsive drug release. Then, CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848. Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs. More importantly, CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model. The mechanistic study demonstrated that CpG@MSNs-R@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells. It was concluded that in comparison to single agonist, the co-delivery of dual agonists, CpG and R848, can improve anti-tumor immune responses for cancer immunotherapy. © Tsinghua University Press 2022 |
abstractGer |
Abstract In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy. Here, we designed a lipid-coated mesoporous silica nanoparticle (MSNsLipo) for the co-delivery of TLR7/8 agonist resiquimod (R848) and TLR9 agonist CpG oligodeoxynucleotides (ODNs) (CpG@MSNs-R@L-M). R848 was firstly conjugated onto the nanoparticle via silane chemistry, which is acidic responsive drug release. Then, CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848. Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs. More importantly, CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model. The mechanistic study demonstrated that CpG@MSNs-R@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells. It was concluded that in comparison to single agonist, the co-delivery of dual agonists, CpG and R848, can improve anti-tumor immune responses for cancer immunotherapy. © Tsinghua University Press 2022 |
abstract_unstemmed |
Abstract In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy. Here, we designed a lipid-coated mesoporous silica nanoparticle (MSNsLipo) for the co-delivery of TLR7/8 agonist resiquimod (R848) and TLR9 agonist CpG oligodeoxynucleotides (ODNs) (CpG@MSNs-R@L-M). R848 was firstly conjugated onto the nanoparticle via silane chemistry, which is acidic responsive drug release. Then, CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848. Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs. More importantly, CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model. The mechanistic study demonstrated that CpG@MSNs-R@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells. It was concluded that in comparison to single agonist, the co-delivery of dual agonists, CpG and R848, can improve anti-tumor immune responses for cancer immunotherapy. © Tsinghua University Press 2022 |
collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 |
container_issue |
9 |
title_short |
Systematic co-delivery of dual agonists to enhance cancer immunotherapy |
url |
https://dx.doi.org/10.1007/s12274-022-4504-2 |
remote_bool |
true |
author2 |
Chen, Guiyuan Wang, Yangyi Su, Lanhong Chen, Bo Wu, Kecheng Xing, Yun Song, Zechenxi Dai, Ruike Liu, Tianxin Zhao, Jiaao Xie, Zhe Zhou, Peijie Xia, Xiaoping Min, Yuanzeng |
author2Str |
Chen, Guiyuan Wang, Yangyi Su, Lanhong Chen, Bo Wu, Kecheng Xing, Yun Song, Zechenxi Dai, Ruike Liu, Tianxin Zhao, Jiaao Xie, Zhe Zhou, Peijie Xia, Xiaoping Min, Yuanzeng |
ppnlink |
57375361X |
mediatype_str_mv |
c |
isOA_txt |
false |
hochschulschrift_bool |
false |
doi_str |
10.1007/s12274-022-4504-2 |
up_date |
2024-07-03T18:42:19.888Z |
_version_ |
1803584421119393792 |
fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR050931016</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230509105955.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230508s2022 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s12274-022-4504-2</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR050931016</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s12274-022-4504-2-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Li, Xiangxia</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Systematic co-delivery of dual agonists to enhance cancer immunotherapy</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2022</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© Tsinghua University Press 2022</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy. Here, we designed a lipid-coated mesoporous silica nanoparticle (MSNsLipo) for the co-delivery of TLR7/8 agonist resiquimod (R848) and TLR9 agonist CpG oligodeoxynucleotides (ODNs) (CpG@MSNs-R@L-M). R848 was firstly conjugated onto the nanoparticle via silane chemistry, which is acidic responsive drug release. Then, CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848. Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs. More importantly, CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model. The mechanistic study demonstrated that CpG@MSNs-R@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells. It was concluded that in comparison to single agonist, the co-delivery of dual agonists, CpG and R848, can improve anti-tumor immune responses for cancer immunotherapy.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">toll-like receptors (TLRs) agonists</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">mesoporous silica nanoparticles (MSNs)</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">drug delivery</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">tumor immunosuppressive microenvironment (TIME)</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">cancer immunotherapy</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Chen, Guiyuan</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wang, Yangyi</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Su, Lanhong</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Chen, Bo</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wu, Kecheng</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Xing, Yun</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Song, Zechenxi</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dai, Ruike</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Liu, Tianxin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhao, Jiaao</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Xie, Zhe</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhou, Peijie</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Xia, Xiaoping</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Min, Yuanzeng</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Nano research</subfield><subfield code="d">[S.l.] : Tsinghua Press, 2008</subfield><subfield code="g">15(2022), 9 vom: 20. Juni, Seite 8326-8335</subfield><subfield code="w">(DE-627)57375361X</subfield><subfield code="w">(DE-600)2442216-2</subfield><subfield code="x">1998-0000</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:15</subfield><subfield code="g">year:2022</subfield><subfield code="g">number:9</subfield><subfield code="g">day:20</subfield><subfield code="g">month:06</subfield><subfield code="g">pages:8326-8335</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1007/s12274-022-4504-2</subfield><subfield code="z">lizenzpflichtig</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_32</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_90</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_100</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_101</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_120</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_138</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_150</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_152</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_171</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_187</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_224</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_250</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_281</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_370</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_636</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_702</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2001</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2004</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2006</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2007</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2008</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2010</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2011</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2015</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2020</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2021</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2025</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2026</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2027</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2031</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2034</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2038</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2039</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2044</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2048</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2049</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2050</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2056</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2057</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2059</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2061</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2064</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2065</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2068</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2088</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2093</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2106</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2107</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2108</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2113</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2118</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2122</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2129</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2143</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2144</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2147</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2148</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2152</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2153</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2188</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2190</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2232</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2336</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2446</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2470</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2472</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2507</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2522</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2548</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4035</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4046</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4242</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4246</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4251</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4326</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4328</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4333</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4334</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4335</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4336</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4393</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">15</subfield><subfield code="j">2022</subfield><subfield code="e">9</subfield><subfield code="b">20</subfield><subfield code="c">06</subfield><subfield code="h">8326-8335</subfield></datafield></record></collection>
|
score |
7.400613 |