Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance

Abstract Background Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Weixi Jiang [verfasserIn] Lei Su [verfasserIn] Meng Ao [verfasserIn] Xun Guo [verfasserIn] Chen Cheng [verfasserIn] Yuanli Luo [verfasserIn] Zhuoyan Xie [verfasserIn] Xingyue Wang [verfasserIn] Junrui Wang [verfasserIn] Shuling Liu [verfasserIn] Yang Cao [verfasserIn] Pan Li [verfasserIn] Zhigang Wang [verfasserIn] Haitao Ran [verfasserIn] Zhiyi Zhou [verfasserIn] Jianli Ren [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	Multidrug resistance Endo/lysosomal escape Tumor homing-penetrating peptide Chemotherapy enhancement PD-L1 blockade

Übergeordnetes Werk:	In: Journal of Nanobiotechnology - BMC, 2003, 19(2021), 1, Seite 23
Übergeordnetes Werk:	volume:19 ; year:2021 ; number:1 ; pages:23

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12951-021-00947-9

Katalog-ID:	DOAJ086779737

Internformat


LEADER	01000caa a22002652 4500
001	DOAJ086779737
003	DE-627
005	20230502152517.0
007	cr uuu---uuuuu
008	230311s2021 xx \|\|\|\|\|o 00\| \|\|eng c
024	7		\|a 10.1186/s12951-021-00947-9 \|2 doi
035			\|a (DE-627)DOAJ086779737
035			\|a (DE-599)DOAJaa5b34217f1c41658cc6b2acc00741d0
040			\|a DE-627 \|b ger \|c DE-627 \|e rakwb
041			\|a eng
050		0	\|a TP248.13-248.65
050		0	\|a R855-855.5
100	0		\|a Weixi Jiang \|e verfasserin \|4 aut
245	1	0	\|a Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance
264		1	\|c 2021
336			\|a Text \|b txt \|2 rdacontent
337			\|a Computermedien \|b c \|2 rdamedia
338			\|a Online-Ressource \|b cr \|2 rdacarrier
520			\|a Abstract Background Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. Results In this study, we fabricated a “combo” nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. Conclusion This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel. Graphic Abstract
650		4	\|a Multidrug resistance
650		4	\|a Endo/lysosomal escape
650		4	\|a Tumor homing-penetrating peptide
650		4	\|a Chemotherapy enhancement
650		4	\|a PD-L1 blockade
653		0	\|a Biotechnology
653		0	\|a Medical technology
700	0		\|a Lei Su \|e verfasserin \|4 aut
700	0		\|a Meng Ao \|e verfasserin \|4 aut
700	0		\|a Xun Guo \|e verfasserin \|4 aut
700	0		\|a Chen Cheng \|e verfasserin \|4 aut
700	0		\|a Yuanli Luo \|e verfasserin \|4 aut
700	0		\|a Zhuoyan Xie \|e verfasserin \|4 aut
700	0		\|a Xingyue Wang \|e verfasserin \|4 aut
700	0		\|a Junrui Wang \|e verfasserin \|4 aut
700	0		\|a Shuling Liu \|e verfasserin \|4 aut
700	0		\|a Yang Cao \|e verfasserin \|4 aut
700	0		\|a Pan Li \|e verfasserin \|4 aut
700	0		\|a Zhigang Wang \|e verfasserin \|4 aut
700	0		\|a Haitao Ran \|e verfasserin \|4 aut
700	0		\|a Zhiyi Zhou \|e verfasserin \|4 aut
700	0		\|a Jianli Ren \|e verfasserin \|4 aut
773	0	8	\|i In \|t Journal of Nanobiotechnology \|d BMC, 2003 \|g 19(2021), 1, Seite 23 \|w (DE-627)362770328 \|w (DE-600)2100022-0 \|x 14773155 \|7 nnns
773	1	8	\|g volume:19 \|g year:2021 \|g number:1 \|g pages:23
856	4	0	\|u https://doi.org/10.1186/s12951-021-00947-9 \|z kostenfrei
856	4	0	\|u https://doaj.org/article/aa5b34217f1c41658cc6b2acc00741d0 \|z kostenfrei
856	4	0	\|u https://doi.org/10.1186/s12951-021-00947-9 \|z kostenfrei
856	4	2	\|u https://doaj.org/toc/1477-3155 \|y Journal toc \|z kostenfrei
912			\|a GBV_USEFLAG_A
912			\|a SYSFLAG_A
912			\|a GBV_DOAJ
912			\|a SSG-OLC-PHA
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_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_95
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_151
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
912			\|a GBV_ILN_206
912			\|a GBV_ILN_213
912			\|a GBV_ILN_230
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_602
912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2009
912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2027
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2108
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_2119
912			\|a GBV_ILN_4012
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4249
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_4338
912			\|a GBV_ILN_4367
912			\|a GBV_ILN_4700
951			\|a AR
952			\|d 19 \|j 2021 \|e 1 \|h 23

Indexfelder

author_variant	w j wj l s ls m a ma x g xg c c cc y l yl z x zx x w xw j w jw s l sl y c yc p l pl z w zw h r hr z z zz j r jr
matchkey_str	article:14773155:2021----::mlfeattmrfiayytreedurtninnceoestztosrtgbsdobnnaetoehrihd1
hierarchy_sort_str	2021
callnumber-subject-code	TP
publishDate	2021
allfields	10.1186/s12951-021-00947-9 doi (DE-627)DOAJ086779737 (DE-599)DOAJaa5b34217f1c41658cc6b2acc00741d0 DE-627 ger DE-627 rakwb eng TP248.13-248.65 R855-855.5 Weixi Jiang verfasserin aut Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. Results In this study, we fabricated a “combo” nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. Conclusion This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel. Graphic Abstract Multidrug resistance Endo/lysosomal escape Tumor homing-penetrating peptide Chemotherapy enhancement PD-L1 blockade Biotechnology Medical technology Lei Su verfasserin aut Meng Ao verfasserin aut Xun Guo verfasserin aut Chen Cheng verfasserin aut Yuanli Luo verfasserin aut Zhuoyan Xie verfasserin aut Xingyue Wang verfasserin aut Junrui Wang verfasserin aut Shuling Liu verfasserin aut Yang Cao verfasserin aut Pan Li verfasserin aut Zhigang Wang verfasserin aut Haitao Ran verfasserin aut Zhiyi Zhou verfasserin aut Jianli Ren verfasserin aut In Journal of Nanobiotechnology BMC, 2003 19(2021), 1, Seite 23 (DE-627)362770328 (DE-600)2100022-0 14773155 nnns volume:19 year:2021 number:1 pages:23 https://doi.org/10.1186/s12951-021-00947-9 kostenfrei https://doaj.org/article/aa5b34217f1c41658cc6b2acc00741d0 kostenfrei https://doi.org/10.1186/s12951-021-00947-9 kostenfrei https://doaj.org/toc/1477-3155 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2021 1 23
spelling	10.1186/s12951-021-00947-9 doi (DE-627)DOAJ086779737 (DE-599)DOAJaa5b34217f1c41658cc6b2acc00741d0 DE-627 ger DE-627 rakwb eng TP248.13-248.65 R855-855.5 Weixi Jiang verfasserin aut Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. Results In this study, we fabricated a “combo” nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. Conclusion This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel. Graphic Abstract Multidrug resistance Endo/lysosomal escape Tumor homing-penetrating peptide Chemotherapy enhancement PD-L1 blockade Biotechnology Medical technology Lei Su verfasserin aut Meng Ao verfasserin aut Xun Guo verfasserin aut Chen Cheng verfasserin aut Yuanli Luo verfasserin aut Zhuoyan Xie verfasserin aut Xingyue Wang verfasserin aut Junrui Wang verfasserin aut Shuling Liu verfasserin aut Yang Cao verfasserin aut Pan Li verfasserin aut Zhigang Wang verfasserin aut Haitao Ran verfasserin aut Zhiyi Zhou verfasserin aut Jianli Ren verfasserin aut In Journal of Nanobiotechnology BMC, 2003 19(2021), 1, Seite 23 (DE-627)362770328 (DE-600)2100022-0 14773155 nnns volume:19 year:2021 number:1 pages:23 https://doi.org/10.1186/s12951-021-00947-9 kostenfrei https://doaj.org/article/aa5b34217f1c41658cc6b2acc00741d0 kostenfrei https://doi.org/10.1186/s12951-021-00947-9 kostenfrei https://doaj.org/toc/1477-3155 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2021 1 23
allfields_unstemmed	10.1186/s12951-021-00947-9 doi (DE-627)DOAJ086779737 (DE-599)DOAJaa5b34217f1c41658cc6b2acc00741d0 DE-627 ger DE-627 rakwb eng TP248.13-248.65 R855-855.5 Weixi Jiang verfasserin aut Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. Results In this study, we fabricated a “combo” nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. Conclusion This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel. Graphic Abstract Multidrug resistance Endo/lysosomal escape Tumor homing-penetrating peptide Chemotherapy enhancement PD-L1 blockade Biotechnology Medical technology Lei Su verfasserin aut Meng Ao verfasserin aut Xun Guo verfasserin aut Chen Cheng verfasserin aut Yuanli Luo verfasserin aut Zhuoyan Xie verfasserin aut Xingyue Wang verfasserin aut Junrui Wang verfasserin aut Shuling Liu verfasserin aut Yang Cao verfasserin aut Pan Li verfasserin aut Zhigang Wang verfasserin aut Haitao Ran verfasserin aut Zhiyi Zhou verfasserin aut Jianli Ren verfasserin aut In Journal of Nanobiotechnology BMC, 2003 19(2021), 1, Seite 23 (DE-627)362770328 (DE-600)2100022-0 14773155 nnns volume:19 year:2021 number:1 pages:23 https://doi.org/10.1186/s12951-021-00947-9 kostenfrei https://doaj.org/article/aa5b34217f1c41658cc6b2acc00741d0 kostenfrei https://doi.org/10.1186/s12951-021-00947-9 kostenfrei https://doaj.org/toc/1477-3155 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2021 1 23
allfieldsGer	10.1186/s12951-021-00947-9 doi (DE-627)DOAJ086779737 (DE-599)DOAJaa5b34217f1c41658cc6b2acc00741d0 DE-627 ger DE-627 rakwb eng TP248.13-248.65 R855-855.5 Weixi Jiang verfasserin aut Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. Results In this study, we fabricated a “combo” nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. Conclusion This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel. Graphic Abstract Multidrug resistance Endo/lysosomal escape Tumor homing-penetrating peptide Chemotherapy enhancement PD-L1 blockade Biotechnology Medical technology Lei Su verfasserin aut Meng Ao verfasserin aut Xun Guo verfasserin aut Chen Cheng verfasserin aut Yuanli Luo verfasserin aut Zhuoyan Xie verfasserin aut Xingyue Wang verfasserin aut Junrui Wang verfasserin aut Shuling Liu verfasserin aut Yang Cao verfasserin aut Pan Li verfasserin aut Zhigang Wang verfasserin aut Haitao Ran verfasserin aut Zhiyi Zhou verfasserin aut Jianli Ren verfasserin aut In Journal of Nanobiotechnology BMC, 2003 19(2021), 1, Seite 23 (DE-627)362770328 (DE-600)2100022-0 14773155 nnns volume:19 year:2021 number:1 pages:23 https://doi.org/10.1186/s12951-021-00947-9 kostenfrei https://doaj.org/article/aa5b34217f1c41658cc6b2acc00741d0 kostenfrei https://doi.org/10.1186/s12951-021-00947-9 kostenfrei https://doaj.org/toc/1477-3155 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2021 1 23
allfieldsSound	10.1186/s12951-021-00947-9 doi (DE-627)DOAJ086779737 (DE-599)DOAJaa5b34217f1c41658cc6b2acc00741d0 DE-627 ger DE-627 rakwb eng TP248.13-248.65 R855-855.5 Weixi Jiang verfasserin aut Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. Results In this study, we fabricated a “combo” nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. Conclusion This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel. Graphic Abstract Multidrug resistance Endo/lysosomal escape Tumor homing-penetrating peptide Chemotherapy enhancement PD-L1 blockade Biotechnology Medical technology Lei Su verfasserin aut Meng Ao verfasserin aut Xun Guo verfasserin aut Chen Cheng verfasserin aut Yuanli Luo verfasserin aut Zhuoyan Xie verfasserin aut Xingyue Wang verfasserin aut Junrui Wang verfasserin aut Shuling Liu verfasserin aut Yang Cao verfasserin aut Pan Li verfasserin aut Zhigang Wang verfasserin aut Haitao Ran verfasserin aut Zhiyi Zhou verfasserin aut Jianli Ren verfasserin aut In Journal of Nanobiotechnology BMC, 2003 19(2021), 1, Seite 23 (DE-627)362770328 (DE-600)2100022-0 14773155 nnns volume:19 year:2021 number:1 pages:23 https://doi.org/10.1186/s12951-021-00947-9 kostenfrei https://doaj.org/article/aa5b34217f1c41658cc6b2acc00741d0 kostenfrei https://doi.org/10.1186/s12951-021-00947-9 kostenfrei https://doaj.org/toc/1477-3155 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 19 2021 1 23
language	English
source	In Journal of Nanobiotechnology 19(2021), 1, Seite 23 volume:19 year:2021 number:1 pages:23
sourceStr	In Journal of Nanobiotechnology 19(2021), 1, Seite 23 volume:19 year:2021 number:1 pages:23
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Multidrug resistance Endo/lysosomal escape Tumor homing-penetrating peptide Chemotherapy enhancement PD-L1 blockade Biotechnology Medical technology
isfreeaccess_bool	true
container_title	Journal of Nanobiotechnology
authorswithroles_txt_mv	Weixi Jiang @@aut@@ Lei Su @@aut@@ Meng Ao @@aut@@ Xun Guo @@aut@@ Chen Cheng @@aut@@ Yuanli Luo @@aut@@ Zhuoyan Xie @@aut@@ Xingyue Wang @@aut@@ Junrui Wang @@aut@@ Shuling Liu @@aut@@ Yang Cao @@aut@@ Pan Li @@aut@@ Zhigang Wang @@aut@@ Haitao Ran @@aut@@ Zhiyi Zhou @@aut@@ Jianli Ren @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	362770328
id	DOAJ086779737
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">DOAJ086779737</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230502152517.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230311s2021 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s12951-021-00947-9</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ086779737</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJaa5b34217f1c41658cc6b2acc00741d0</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="050" ind1=" " ind2="0"><subfield code="a">TP248.13-248.65</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">R855-855.5</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Weixi Jiang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2021</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="520" ind1=" " ind2=" "><subfield code="a">Abstract Background Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. Results In this study, we fabricated a “combo” nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. Conclusion This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel. Graphic Abstract</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Multidrug resistance</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Endo/lysosomal escape</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tumor homing-penetrating peptide</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Chemotherapy enhancement</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">PD-L1 blockade</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Biotechnology</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medical technology</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lei Su</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Meng Ao</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xun Guo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Chen Cheng</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yuanli Luo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Zhuoyan Xie</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xingyue Wang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Junrui Wang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Shuling Liu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yang Cao</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pan Li</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Zhigang Wang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Haitao Ran</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Zhiyi Zhou</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jianli Ren</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Journal of Nanobiotechnology</subfield><subfield code="d">BMC, 2003</subfield><subfield code="g">19(2021), 1, Seite 23</subfield><subfield code="w">(DE-627)362770328</subfield><subfield code="w">(DE-600)2100022-0</subfield><subfield code="x">14773155</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:19</subfield><subfield code="g">year:2021</subfield><subfield code="g">number:1</subfield><subfield code="g">pages:23</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1186/s12951-021-00947-9</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/aa5b34217f1c41658cc6b2acc00741d0</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1186/s12951-021-00947-9</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1477-3155</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</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_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</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_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_95</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_151</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_206</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_230</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_602</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_2005</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_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_2027</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_2108</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_2119</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</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_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_4249</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_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</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">19</subfield><subfield code="j">2021</subfield><subfield code="e">1</subfield><subfield code="h">23</subfield></datafield></record></collection>
callnumber-first	T - Technology
author	Weixi Jiang
spellingShingle	Weixi Jiang misc TP248.13-248.65 misc R855-855.5 misc Multidrug resistance misc Endo/lysosomal escape misc Tumor homing-penetrating peptide misc Chemotherapy enhancement misc PD-L1 blockade misc Biotechnology misc Medical technology Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance
authorStr	Weixi Jiang
ppnlink_with_tag_str_mv	@@773@@(DE-627)362770328
format	electronic Article
delete_txt_mv	keep
author_role	aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut
collection	DOAJ
remote_str	true
callnumber-label	TP248
illustrated	Not Illustrated
issn	14773155
topic_title	TP248.13-248.65 R855-855.5 Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance Multidrug resistance Endo/lysosomal escape Tumor homing-penetrating peptide Chemotherapy enhancement PD-L1 blockade
topic	misc TP248.13-248.65 misc R855-855.5 misc Multidrug resistance misc Endo/lysosomal escape misc Tumor homing-penetrating peptide misc Chemotherapy enhancement misc PD-L1 blockade misc Biotechnology misc Medical technology
topic_unstemmed	misc TP248.13-248.65 misc R855-855.5 misc Multidrug resistance misc Endo/lysosomal escape misc Tumor homing-penetrating peptide misc Chemotherapy enhancement misc PD-L1 blockade misc Biotechnology misc Medical technology
topic_browse	misc TP248.13-248.65 misc R855-855.5 misc Multidrug resistance misc Endo/lysosomal escape misc Tumor homing-penetrating peptide misc Chemotherapy enhancement misc PD-L1 blockade misc Biotechnology misc Medical technology
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
format_main_str_mv	Text Zeitschrift/Artikel
carriertype_str_mv	cr
hierarchy_parent_title	Journal of Nanobiotechnology
hierarchy_parent_id	362770328
hierarchy_top_title	Journal of Nanobiotechnology
isfreeaccess_txt	true
familylinks_str_mv	(DE-627)362770328 (DE-600)2100022-0
title	Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance
ctrlnum	(DE-627)DOAJ086779737 (DE-599)DOAJaa5b34217f1c41658cc6b2acc00741d0
title_full	Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance
author_sort	Weixi Jiang
journal	Journal of Nanobiotechnology
journalStr	Journal of Nanobiotechnology
callnumber-first-code	T
lang_code	eng
isOA_bool	true
recordtype	marc
publishDateSort	2021
contenttype_str_mv	txt
container_start_page	23
author_browse	Weixi Jiang Lei Su Meng Ao Xun Guo Chen Cheng Yuanli Luo Zhuoyan Xie Xingyue Wang Junrui Wang Shuling Liu Yang Cao Pan Li Zhigang Wang Haitao Ran Zhiyi Zhou Jianli Ren
container_volume	19
class	TP248.13-248.65 R855-855.5
format_se	Elektronische Aufsätze
author-letter	Weixi Jiang
doi_str_mv	10.1186/s12951-021-00947-9
author2-role	verfasserin
title_sort	amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with pd-l1 blockade in reversing multidrug resistance
callnumber	TP248.13-248.65
title_auth	Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance
abstract	Abstract Background Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. Results In this study, we fabricated a “combo” nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. Conclusion This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel. Graphic Abstract
abstractGer	Abstract Background Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. Results In this study, we fabricated a “combo” nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. Conclusion This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel. Graphic Abstract
abstract_unstemmed	Abstract Background Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. Results In this study, we fabricated a “combo” nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. Conclusion This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel. Graphic Abstract
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2119 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700
container_issue	1
title_short	Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance
url	https://doi.org/10.1186/s12951-021-00947-9 https://doaj.org/article/aa5b34217f1c41658cc6b2acc00741d0 https://doaj.org/toc/1477-3155
remote_bool	true
author2	Lei Su Meng Ao Xun Guo Chen Cheng Yuanli Luo Zhuoyan Xie Xingyue Wang Junrui Wang Shuling Liu Yang Cao Pan Li Zhigang Wang Haitao Ran Zhiyi Zhou Jianli Ren
author2Str	Lei Su Meng Ao Xun Guo Chen Cheng Yuanli Luo Zhuoyan Xie Xingyue Wang Junrui Wang Shuling Liu Yang Cao Pan Li Zhigang Wang Haitao Ran Zhiyi Zhou Jianli Ren
ppnlink	362770328
callnumber-subject	TP - Chemical Technology
mediatype_str_mv	c
isOA_txt	true
hochschulschrift_bool	false
doi_str	10.1186/s12951-021-00947-9
callnumber-a	TP248.13-248.65
up_date	2024-07-03T22:42:51.354Z
_version_	1803599553610383360
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">DOAJ086779737</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230502152517.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230311s2021 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s12951-021-00947-9</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ086779737</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJaa5b34217f1c41658cc6b2acc00741d0</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="050" ind1=" " ind2="0"><subfield code="a">TP248.13-248.65</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">R855-855.5</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Weixi Jiang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2021</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="520" ind1=" " ind2=" "><subfield code="a">Abstract Background Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. Results In this study, we fabricated a “combo” nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. Conclusion This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel. Graphic Abstract</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Multidrug resistance</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Endo/lysosomal escape</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tumor homing-penetrating peptide</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Chemotherapy enhancement</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">PD-L1 blockade</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Biotechnology</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medical technology</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lei Su</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Meng Ao</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xun Guo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Chen Cheng</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yuanli Luo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Zhuoyan Xie</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xingyue Wang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Junrui Wang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Shuling Liu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yang Cao</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pan Li</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Zhigang Wang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Haitao Ran</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Zhiyi Zhou</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jianli Ren</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Journal of Nanobiotechnology</subfield><subfield code="d">BMC, 2003</subfield><subfield code="g">19(2021), 1, Seite 23</subfield><subfield code="w">(DE-627)362770328</subfield><subfield code="w">(DE-600)2100022-0</subfield><subfield code="x">14773155</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:19</subfield><subfield code="g">year:2021</subfield><subfield code="g">number:1</subfield><subfield code="g">pages:23</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1186/s12951-021-00947-9</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/aa5b34217f1c41658cc6b2acc00741d0</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1186/s12951-021-00947-9</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1477-3155</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</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_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</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_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_95</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_151</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_206</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_230</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_602</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_2005</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_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_2027</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_2108</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_2119</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</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_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_4249</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_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</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">19</subfield><subfield code="j">2021</subfield><subfield code="e">1</subfield><subfield code="h">23</subfield></datafield></record></collection>
score	7.3996735

Nicht das Richtige dabei?

Schreiben Sie uns!

Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based “combo” nanoagent together with PD-L1 blockade in reversing multidrug resistance

Nicht das Richtige dabei?

Zugang & Verfügbarkeit

Vorhandene Bände

Nicht das Richtige dabei?