Modified Fe3O4 Magnetic Nanoparticle Delivery of CpG Inhibits Tumor Growth and Spontaneous Pulmonary Metastases to Enhance Immunotherapy

Abstract As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeutic agents or vaccine adjuvants for the treatment of cancer. However, some drawbacks of CpG li...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Xueyan Zhang [verfasserIn] Fengbo Wu [verfasserIn] Ke Men [verfasserIn] Rong Huang [verfasserIn] Bailin Zhou [verfasserIn] Rui Zhang [verfasserIn] Rui Zou [verfasserIn] Li Yang [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	CpG Magnetic nanoparticles Intratumoral injection Immunotherapy

Übergeordnetes Werk:	In: Nanoscale Research Letters - SpringerOpen, 2007, 13(2018), 1, Seite 12
Übergeordnetes Werk:	volume:13 ; year:2018 ; number:1 ; pages:12

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.1186/s11671-018-2661-8

Katalog-ID:	DOAJ053514726

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520			\|a Abstract As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeutic agents or vaccine adjuvants for the treatment of cancer. However, some drawbacks of CpG limit their applications, such as rapid elimination by nuclease-mediated degradation and poor cellular uptake. Therefore, repeat high-dose drug administration is required for treatment. In this work, a CpG delivery system based on 3-aminopropyltriethoxysilane (APTES)-modified Fe3O4 nanoparticles (FeNPs) was designed and studied for the first time to achieve better bioactivity of CpG. In our results, we designed FeNP-delivered CpG particles (FeNP/CpG) with a small average size of approximately 50 nm by loading CpG into FeNPs. The FeNP/CpG particle delivery system, with enhanced cell uptake of CpG in bone marrow-derived dendritic cells (BMDCs) in vitro and through intratumoral injection, showed significant antitumor ability by stimulating better humoral and cellular immune responses in C26 colon cancer and 4T1 breast cancer xenograft models in vivo over those of free CpG. Moreover, mice treated by FeNP/CpG particles had delayed tumor growth with an inhibitory rate as high as 94.4%. In addition, approximately 50% of the tumors in the C26 model appeared to regress completely. Similarly, there were lower pulmonary metastases and a 69% tumor inhibitory rate in the 4T1 breast cancer tumor model than those in the untreated controls. In addition to their effectiveness, the easy preparation, safety, and high stability of FeNP/CpG particles also make them an attractive antitumor immunotherapy.
650		4	\|a CpG
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650		4	\|a Immunotherapy
653		0	\|a Materials of engineering and construction. Mechanics of materials
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700	0		\|a Li Yang \|e verfasserin \|4 aut
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allfields	10.1186/s11671-018-2661-8 doi (DE-627)DOAJ053514726 (DE-599)DOAJd40db87bbbec492e82e1650608e2ec88 DE-627 ger DE-627 rakwb eng TA401-492 Xueyan Zhang verfasserin aut Modified Fe3O4 Magnetic Nanoparticle Delivery of CpG Inhibits Tumor Growth and Spontaneous Pulmonary Metastases to Enhance Immunotherapy 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeutic agents or vaccine adjuvants for the treatment of cancer. However, some drawbacks of CpG limit their applications, such as rapid elimination by nuclease-mediated degradation and poor cellular uptake. Therefore, repeat high-dose drug administration is required for treatment. In this work, a CpG delivery system based on 3-aminopropyltriethoxysilane (APTES)-modified Fe3O4 nanoparticles (FeNPs) was designed and studied for the first time to achieve better bioactivity of CpG. In our results, we designed FeNP-delivered CpG particles (FeNP/CpG) with a small average size of approximately 50 nm by loading CpG into FeNPs. The FeNP/CpG particle delivery system, with enhanced cell uptake of CpG in bone marrow-derived dendritic cells (BMDCs) in vitro and through intratumoral injection, showed significant antitumor ability by stimulating better humoral and cellular immune responses in C26 colon cancer and 4T1 breast cancer xenograft models in vivo over those of free CpG. Moreover, mice treated by FeNP/CpG particles had delayed tumor growth with an inhibitory rate as high as 94.4%. In addition, approximately 50% of the tumors in the C26 model appeared to regress completely. Similarly, there were lower pulmonary metastases and a 69% tumor inhibitory rate in the 4T1 breast cancer tumor model than those in the untreated controls. In addition to their effectiveness, the easy preparation, safety, and high stability of FeNP/CpG particles also make them an attractive antitumor immunotherapy. CpG Magnetic nanoparticles Intratumoral injection Immunotherapy Materials of engineering and construction. Mechanics of materials Fengbo Wu verfasserin aut Ke Men verfasserin aut Rong Huang verfasserin aut Bailin Zhou verfasserin aut Rui Zhang verfasserin aut Rui Zou verfasserin aut Li Yang verfasserin aut In Nanoscale Research Letters SpringerOpen, 2007 13(2018), 1, Seite 12 (DE-627)518632474 (DE-600)2253244-4 1556276X nnns volume:13 year:2018 number:1 pages:12 https://doi.org/10.1186/s11671-018-2661-8 kostenfrei https://doaj.org/article/d40db87bbbec492e82e1650608e2ec88 kostenfrei http://link.springer.com/article/10.1186/s11671-018-2661-8 kostenfrei https://doaj.org/toc/1931-7573 Journal toc kostenfrei https://doaj.org/toc/1556-276X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 1 12
spelling	10.1186/s11671-018-2661-8 doi (DE-627)DOAJ053514726 (DE-599)DOAJd40db87bbbec492e82e1650608e2ec88 DE-627 ger DE-627 rakwb eng TA401-492 Xueyan Zhang verfasserin aut Modified Fe3O4 Magnetic Nanoparticle Delivery of CpG Inhibits Tumor Growth and Spontaneous Pulmonary Metastases to Enhance Immunotherapy 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeutic agents or vaccine adjuvants for the treatment of cancer. However, some drawbacks of CpG limit their applications, such as rapid elimination by nuclease-mediated degradation and poor cellular uptake. Therefore, repeat high-dose drug administration is required for treatment. In this work, a CpG delivery system based on 3-aminopropyltriethoxysilane (APTES)-modified Fe3O4 nanoparticles (FeNPs) was designed and studied for the first time to achieve better bioactivity of CpG. In our results, we designed FeNP-delivered CpG particles (FeNP/CpG) with a small average size of approximately 50 nm by loading CpG into FeNPs. The FeNP/CpG particle delivery system, with enhanced cell uptake of CpG in bone marrow-derived dendritic cells (BMDCs) in vitro and through intratumoral injection, showed significant antitumor ability by stimulating better humoral and cellular immune responses in C26 colon cancer and 4T1 breast cancer xenograft models in vivo over those of free CpG. Moreover, mice treated by FeNP/CpG particles had delayed tumor growth with an inhibitory rate as high as 94.4%. In addition, approximately 50% of the tumors in the C26 model appeared to regress completely. Similarly, there were lower pulmonary metastases and a 69% tumor inhibitory rate in the 4T1 breast cancer tumor model than those in the untreated controls. In addition to their effectiveness, the easy preparation, safety, and high stability of FeNP/CpG particles also make them an attractive antitumor immunotherapy. CpG Magnetic nanoparticles Intratumoral injection Immunotherapy Materials of engineering and construction. Mechanics of materials Fengbo Wu verfasserin aut Ke Men verfasserin aut Rong Huang verfasserin aut Bailin Zhou verfasserin aut Rui Zhang verfasserin aut Rui Zou verfasserin aut Li Yang verfasserin aut In Nanoscale Research Letters SpringerOpen, 2007 13(2018), 1, Seite 12 (DE-627)518632474 (DE-600)2253244-4 1556276X nnns volume:13 year:2018 number:1 pages:12 https://doi.org/10.1186/s11671-018-2661-8 kostenfrei https://doaj.org/article/d40db87bbbec492e82e1650608e2ec88 kostenfrei http://link.springer.com/article/10.1186/s11671-018-2661-8 kostenfrei https://doaj.org/toc/1931-7573 Journal toc kostenfrei https://doaj.org/toc/1556-276X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 1 12
allfields_unstemmed	10.1186/s11671-018-2661-8 doi (DE-627)DOAJ053514726 (DE-599)DOAJd40db87bbbec492e82e1650608e2ec88 DE-627 ger DE-627 rakwb eng TA401-492 Xueyan Zhang verfasserin aut Modified Fe3O4 Magnetic Nanoparticle Delivery of CpG Inhibits Tumor Growth and Spontaneous Pulmonary Metastases to Enhance Immunotherapy 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeutic agents or vaccine adjuvants for the treatment of cancer. However, some drawbacks of CpG limit their applications, such as rapid elimination by nuclease-mediated degradation and poor cellular uptake. Therefore, repeat high-dose drug administration is required for treatment. In this work, a CpG delivery system based on 3-aminopropyltriethoxysilane (APTES)-modified Fe3O4 nanoparticles (FeNPs) was designed and studied for the first time to achieve better bioactivity of CpG. In our results, we designed FeNP-delivered CpG particles (FeNP/CpG) with a small average size of approximately 50 nm by loading CpG into FeNPs. The FeNP/CpG particle delivery system, with enhanced cell uptake of CpG in bone marrow-derived dendritic cells (BMDCs) in vitro and through intratumoral injection, showed significant antitumor ability by stimulating better humoral and cellular immune responses in C26 colon cancer and 4T1 breast cancer xenograft models in vivo over those of free CpG. Moreover, mice treated by FeNP/CpG particles had delayed tumor growth with an inhibitory rate as high as 94.4%. In addition, approximately 50% of the tumors in the C26 model appeared to regress completely. Similarly, there were lower pulmonary metastases and a 69% tumor inhibitory rate in the 4T1 breast cancer tumor model than those in the untreated controls. In addition to their effectiveness, the easy preparation, safety, and high stability of FeNP/CpG particles also make them an attractive antitumor immunotherapy. CpG Magnetic nanoparticles Intratumoral injection Immunotherapy Materials of engineering and construction. Mechanics of materials Fengbo Wu verfasserin aut Ke Men verfasserin aut Rong Huang verfasserin aut Bailin Zhou verfasserin aut Rui Zhang verfasserin aut Rui Zou verfasserin aut Li Yang verfasserin aut In Nanoscale Research Letters SpringerOpen, 2007 13(2018), 1, Seite 12 (DE-627)518632474 (DE-600)2253244-4 1556276X nnns volume:13 year:2018 number:1 pages:12 https://doi.org/10.1186/s11671-018-2661-8 kostenfrei https://doaj.org/article/d40db87bbbec492e82e1650608e2ec88 kostenfrei http://link.springer.com/article/10.1186/s11671-018-2661-8 kostenfrei https://doaj.org/toc/1931-7573 Journal toc kostenfrei https://doaj.org/toc/1556-276X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 1 12
allfieldsGer	10.1186/s11671-018-2661-8 doi (DE-627)DOAJ053514726 (DE-599)DOAJd40db87bbbec492e82e1650608e2ec88 DE-627 ger DE-627 rakwb eng TA401-492 Xueyan Zhang verfasserin aut Modified Fe3O4 Magnetic Nanoparticle Delivery of CpG Inhibits Tumor Growth and Spontaneous Pulmonary Metastases to Enhance Immunotherapy 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeutic agents or vaccine adjuvants for the treatment of cancer. However, some drawbacks of CpG limit their applications, such as rapid elimination by nuclease-mediated degradation and poor cellular uptake. Therefore, repeat high-dose drug administration is required for treatment. In this work, a CpG delivery system based on 3-aminopropyltriethoxysilane (APTES)-modified Fe3O4 nanoparticles (FeNPs) was designed and studied for the first time to achieve better bioactivity of CpG. In our results, we designed FeNP-delivered CpG particles (FeNP/CpG) with a small average size of approximately 50 nm by loading CpG into FeNPs. The FeNP/CpG particle delivery system, with enhanced cell uptake of CpG in bone marrow-derived dendritic cells (BMDCs) in vitro and through intratumoral injection, showed significant antitumor ability by stimulating better humoral and cellular immune responses in C26 colon cancer and 4T1 breast cancer xenograft models in vivo over those of free CpG. Moreover, mice treated by FeNP/CpG particles had delayed tumor growth with an inhibitory rate as high as 94.4%. In addition, approximately 50% of the tumors in the C26 model appeared to regress completely. Similarly, there were lower pulmonary metastases and a 69% tumor inhibitory rate in the 4T1 breast cancer tumor model than those in the untreated controls. In addition to their effectiveness, the easy preparation, safety, and high stability of FeNP/CpG particles also make them an attractive antitumor immunotherapy. CpG Magnetic nanoparticles Intratumoral injection Immunotherapy Materials of engineering and construction. Mechanics of materials Fengbo Wu verfasserin aut Ke Men verfasserin aut Rong Huang verfasserin aut Bailin Zhou verfasserin aut Rui Zhang verfasserin aut Rui Zou verfasserin aut Li Yang verfasserin aut In Nanoscale Research Letters SpringerOpen, 2007 13(2018), 1, Seite 12 (DE-627)518632474 (DE-600)2253244-4 1556276X nnns volume:13 year:2018 number:1 pages:12 https://doi.org/10.1186/s11671-018-2661-8 kostenfrei https://doaj.org/article/d40db87bbbec492e82e1650608e2ec88 kostenfrei http://link.springer.com/article/10.1186/s11671-018-2661-8 kostenfrei https://doaj.org/toc/1931-7573 Journal toc kostenfrei https://doaj.org/toc/1556-276X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 1 12
allfieldsSound	10.1186/s11671-018-2661-8 doi (DE-627)DOAJ053514726 (DE-599)DOAJd40db87bbbec492e82e1650608e2ec88 DE-627 ger DE-627 rakwb eng TA401-492 Xueyan Zhang verfasserin aut Modified Fe3O4 Magnetic Nanoparticle Delivery of CpG Inhibits Tumor Growth and Spontaneous Pulmonary Metastases to Enhance Immunotherapy 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeutic agents or vaccine adjuvants for the treatment of cancer. However, some drawbacks of CpG limit their applications, such as rapid elimination by nuclease-mediated degradation and poor cellular uptake. Therefore, repeat high-dose drug administration is required for treatment. In this work, a CpG delivery system based on 3-aminopropyltriethoxysilane (APTES)-modified Fe3O4 nanoparticles (FeNPs) was designed and studied for the first time to achieve better bioactivity of CpG. In our results, we designed FeNP-delivered CpG particles (FeNP/CpG) with a small average size of approximately 50 nm by loading CpG into FeNPs. The FeNP/CpG particle delivery system, with enhanced cell uptake of CpG in bone marrow-derived dendritic cells (BMDCs) in vitro and through intratumoral injection, showed significant antitumor ability by stimulating better humoral and cellular immune responses in C26 colon cancer and 4T1 breast cancer xenograft models in vivo over those of free CpG. Moreover, mice treated by FeNP/CpG particles had delayed tumor growth with an inhibitory rate as high as 94.4%. In addition, approximately 50% of the tumors in the C26 model appeared to regress completely. Similarly, there were lower pulmonary metastases and a 69% tumor inhibitory rate in the 4T1 breast cancer tumor model than those in the untreated controls. In addition to their effectiveness, the easy preparation, safety, and high stability of FeNP/CpG particles also make them an attractive antitumor immunotherapy. CpG Magnetic nanoparticles Intratumoral injection Immunotherapy Materials of engineering and construction. Mechanics of materials Fengbo Wu verfasserin aut Ke Men verfasserin aut Rong Huang verfasserin aut Bailin Zhou verfasserin aut Rui Zhang verfasserin aut Rui Zou verfasserin aut Li Yang verfasserin aut In Nanoscale Research Letters SpringerOpen, 2007 13(2018), 1, Seite 12 (DE-627)518632474 (DE-600)2253244-4 1556276X nnns volume:13 year:2018 number:1 pages:12 https://doi.org/10.1186/s11671-018-2661-8 kostenfrei https://doaj.org/article/d40db87bbbec492e82e1650608e2ec88 kostenfrei http://link.springer.com/article/10.1186/s11671-018-2661-8 kostenfrei https://doaj.org/toc/1931-7573 Journal toc kostenfrei https://doaj.org/toc/1556-276X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2027 GBV_ILN_2055 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2018 1 12
language	English
source	In Nanoscale Research Letters 13(2018), 1, Seite 12 volume:13 year:2018 number:1 pages:12
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author	Xueyan Zhang
spellingShingle	Xueyan Zhang misc TA401-492 misc CpG misc Magnetic nanoparticles misc Intratumoral injection misc Immunotherapy misc Materials of engineering and construction. Mechanics of materials Modified Fe3O4 Magnetic Nanoparticle Delivery of CpG Inhibits Tumor Growth and Spontaneous Pulmonary Metastases to Enhance Immunotherapy
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topic_title	TA401-492 Modified Fe3O4 Magnetic Nanoparticle Delivery of CpG Inhibits Tumor Growth and Spontaneous Pulmonary Metastases to Enhance Immunotherapy CpG Magnetic nanoparticles Intratumoral injection Immunotherapy
topic	misc TA401-492 misc CpG misc Magnetic nanoparticles misc Intratumoral injection misc Immunotherapy misc Materials of engineering and construction. Mechanics of materials
topic_unstemmed	misc TA401-492 misc CpG misc Magnetic nanoparticles misc Intratumoral injection misc Immunotherapy misc Materials of engineering and construction. Mechanics of materials
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title	Modified Fe3O4 Magnetic Nanoparticle Delivery of CpG Inhibits Tumor Growth and Spontaneous Pulmonary Metastases to Enhance Immunotherapy
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title_sort	modified fe3o4 magnetic nanoparticle delivery of cpg inhibits tumor growth and spontaneous pulmonary metastases to enhance immunotherapy
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title_auth	Modified Fe3O4 Magnetic Nanoparticle Delivery of CpG Inhibits Tumor Growth and Spontaneous Pulmonary Metastases to Enhance Immunotherapy
abstract	Abstract As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeutic agents or vaccine adjuvants for the treatment of cancer. However, some drawbacks of CpG limit their applications, such as rapid elimination by nuclease-mediated degradation and poor cellular uptake. Therefore, repeat high-dose drug administration is required for treatment. In this work, a CpG delivery system based on 3-aminopropyltriethoxysilane (APTES)-modified Fe3O4 nanoparticles (FeNPs) was designed and studied for the first time to achieve better bioactivity of CpG. In our results, we designed FeNP-delivered CpG particles (FeNP/CpG) with a small average size of approximately 50 nm by loading CpG into FeNPs. The FeNP/CpG particle delivery system, with enhanced cell uptake of CpG in bone marrow-derived dendritic cells (BMDCs) in vitro and through intratumoral injection, showed significant antitumor ability by stimulating better humoral and cellular immune responses in C26 colon cancer and 4T1 breast cancer xenograft models in vivo over those of free CpG. Moreover, mice treated by FeNP/CpG particles had delayed tumor growth with an inhibitory rate as high as 94.4%. In addition, approximately 50% of the tumors in the C26 model appeared to regress completely. Similarly, there were lower pulmonary metastases and a 69% tumor inhibitory rate in the 4T1 breast cancer tumor model than those in the untreated controls. In addition to their effectiveness, the easy preparation, safety, and high stability of FeNP/CpG particles also make them an attractive antitumor immunotherapy.
abstractGer	Abstract As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeutic agents or vaccine adjuvants for the treatment of cancer. However, some drawbacks of CpG limit their applications, such as rapid elimination by nuclease-mediated degradation and poor cellular uptake. Therefore, repeat high-dose drug administration is required for treatment. In this work, a CpG delivery system based on 3-aminopropyltriethoxysilane (APTES)-modified Fe3O4 nanoparticles (FeNPs) was designed and studied for the first time to achieve better bioactivity of CpG. In our results, we designed FeNP-delivered CpG particles (FeNP/CpG) with a small average size of approximately 50 nm by loading CpG into FeNPs. The FeNP/CpG particle delivery system, with enhanced cell uptake of CpG in bone marrow-derived dendritic cells (BMDCs) in vitro and through intratumoral injection, showed significant antitumor ability by stimulating better humoral and cellular immune responses in C26 colon cancer and 4T1 breast cancer xenograft models in vivo over those of free CpG. Moreover, mice treated by FeNP/CpG particles had delayed tumor growth with an inhibitory rate as high as 94.4%. In addition, approximately 50% of the tumors in the C26 model appeared to regress completely. Similarly, there were lower pulmonary metastases and a 69% tumor inhibitory rate in the 4T1 breast cancer tumor model than those in the untreated controls. In addition to their effectiveness, the easy preparation, safety, and high stability of FeNP/CpG particles also make them an attractive antitumor immunotherapy.
abstract_unstemmed	Abstract As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeutic agents or vaccine adjuvants for the treatment of cancer. However, some drawbacks of CpG limit their applications, such as rapid elimination by nuclease-mediated degradation and poor cellular uptake. Therefore, repeat high-dose drug administration is required for treatment. In this work, a CpG delivery system based on 3-aminopropyltriethoxysilane (APTES)-modified Fe3O4 nanoparticles (FeNPs) was designed and studied for the first time to achieve better bioactivity of CpG. In our results, we designed FeNP-delivered CpG particles (FeNP/CpG) with a small average size of approximately 50 nm by loading CpG into FeNPs. The FeNP/CpG particle delivery system, with enhanced cell uptake of CpG in bone marrow-derived dendritic cells (BMDCs) in vitro and through intratumoral injection, showed significant antitumor ability by stimulating better humoral and cellular immune responses in C26 colon cancer and 4T1 breast cancer xenograft models in vivo over those of free CpG. Moreover, mice treated by FeNP/CpG particles had delayed tumor growth with an inhibitory rate as high as 94.4%. In addition, approximately 50% of the tumors in the C26 model appeared to regress completely. Similarly, there were lower pulmonary metastases and a 69% tumor inhibitory rate in the 4T1 breast cancer tumor model than those in the untreated controls. In addition to their effectiveness, the easy preparation, safety, and high stability of FeNP/CpG particles also make them an attractive antitumor immunotherapy.
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title_short	Modified Fe3O4 Magnetic Nanoparticle Delivery of CpG Inhibits Tumor Growth and Spontaneous Pulmonary Metastases to Enhance Immunotherapy
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However, some drawbacks of CpG limit their applications, such as rapid elimination by nuclease-mediated degradation and poor cellular uptake. Therefore, repeat high-dose drug administration is required for treatment. In this work, a CpG delivery system based on 3-aminopropyltriethoxysilane (APTES)-modified Fe3O4 nanoparticles (FeNPs) was designed and studied for the first time to achieve better bioactivity of CpG. In our results, we designed FeNP-delivered CpG particles (FeNP/CpG) with a small average size of approximately 50 nm by loading CpG into FeNPs. The FeNP/CpG particle delivery system, with enhanced cell uptake of CpG in bone marrow-derived dendritic cells (BMDCs) in vitro and through intratumoral injection, showed significant antitumor ability by stimulating better humoral and cellular immune responses in C26 colon cancer and 4T1 breast cancer xenograft models in vivo over those of free CpG. Moreover, mice treated by FeNP/CpG particles had delayed tumor growth with an inhibitory rate as high as 94.4%. In addition, approximately 50% of the tumors in the C26 model appeared to regress completely. Similarly, there were lower pulmonary metastases and a 69% tumor inhibitory rate in the 4T1 breast cancer tumor model than those in the untreated controls. In addition to their effectiveness, the easy preparation, safety, and high stability of FeNP/CpG particles also make them an attractive antitumor immunotherapy.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">CpG</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Magnetic nanoparticles</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Intratumoral injection</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Immunotherapy</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Materials of engineering and construction. 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Modified Fe3O4 Magnetic Nanoparticle Delivery of CpG Inhibits Tumor Growth and Spontaneous Pulmonary Metastases to Enhance Immunotherapy

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