Treatment of Colon Cancer by Degradable rrPPC Nano-Conjugates Delivered STAT3 siRNA

Hongjia Zhang,1,* Ke Men,1,* Congbin Pan,1 Yan Gao,1 Jingmei Li,1 Sibei Lei,1 Guonian Zhu,1 Rui Li,1 Yuquan Wei,1 Xingmei Duan2 1State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan Provinc...

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Autores principales:	Zhang H, Men K, Pan C, Gao Y, Li J, Lei S, Zhu G, Li R, Wei Y, Duan X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	rna interfering nanoparticle stat3 colon cancer Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9e3848211ad6468aad4d8c0fa4b36330
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spelling	oai:doaj.org-article:9e3848211ad6468aad4d8c0fa4b363302021-12-02T15:12:17ZTreatment of Colon Cancer by Degradable rrPPC Nano-Conjugates Delivered STAT3 siRNA1178-2013https://doaj.org/article/9e3848211ad6468aad4d8c0fa4b363302020-12-01T00:00:00Zhttps://www.dovepress.com/treatment-of-colon-cancer-by-degradable-rrppc-nano-conjugates-delivere-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hongjia Zhang,1,* Ke Men,1,* Congbin Pan,1 Yan Gao,1 Jingmei Li,1 Sibei Lei,1 Guonian Zhu,1 Rui Li,1 Yuquan Wei,1 Xingmei Duan2 1State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Men StateKey Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaEmail mendingbob@hotmail.comXingmei DuanDepartment of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, People’s Republic of ChinaEmail duanxingmei2003@163.comBackground: Drugs that work based on the mechanism of RNA interference have shown strong potential in cancer gene therapy. Although significant progress has been made in small interfering RNA (siRNA) design and manufacturing, ideal delivery system remains a limitation for the development of siRNA-based drugs. Particularly, it is necessary to focus on parameters including delivery efficiency, stability, and safety when developing siRNA formulations for cancer therapy.Methods: In this work, a novel degradable siRNA delivery system cRGD-R9-PEG-PEI-Cholesterol (rrPPC) was synthesized based on low molecular weight polyethyleneimine (PEI). Functional groups including cholesterol, cell penetrating peptides (CPPs), and poly(ethylene oxide) were introduced to PEI backbone to attain enhanced transfection efficiency and biocompatibility.Results: The synthesized rrPPC was dispersed as nanoparticles in water with an average size of 195 nm and 41.9 mV in potential. rrPPC nanoparticles could efficiently deliver siRNA into C26 clone cancer cells and trigger caveolae-mediated pathway during transmembrane transportation. By loading the signal transducer and activator of transcription 3 (STAT3) targeting siRNA, rrPPC/STAT3 siRNA (rrPPC/siSTAT3) complex demonstrated strong anti-cancer effects in multiple colon cancer models following local delivery. In addition, intravenous (IV) injection of rrPPC/siSTAT3 complex efficiently suppressed lung metastasis tumor progression with ideal in vivo safety.Conclusion: Our results provide evidence that rrPPC nanoparticles constitute a potential candidate vector for siRNA-based colon cancer gene therapy.Keywords: RNA interfering, nanoparticle, STAT3, colon cancerZhang HMen KPan CGao YLi JLei SZhu GLi RWei YDuan XDove Medical Pressarticlerna interferingnanoparticlestat3colon cancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 9875-9890 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	rna interfering nanoparticle stat3 colon cancer Medicine (General) R5-920
spellingShingle	rna interfering nanoparticle stat3 colon cancer Medicine (General) R5-920 Zhang H Men K Pan C Gao Y Li J Lei S Zhu G Li R Wei Y Duan X Treatment of Colon Cancer by Degradable rrPPC Nano-Conjugates Delivered STAT3 siRNA
description	Hongjia Zhang,1,* Ke Men,1,* Congbin Pan,1 Yan Gao,1 Jingmei Li,1 Sibei Lei,1 Guonian Zhu,1 Rui Li,1 Yuquan Wei,1 Xingmei Duan2 1State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Men StateKey Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaEmail mendingbob@hotmail.comXingmei DuanDepartment of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, People’s Republic of ChinaEmail duanxingmei2003@163.comBackground: Drugs that work based on the mechanism of RNA interference have shown strong potential in cancer gene therapy. Although significant progress has been made in small interfering RNA (siRNA) design and manufacturing, ideal delivery system remains a limitation for the development of siRNA-based drugs. Particularly, it is necessary to focus on parameters including delivery efficiency, stability, and safety when developing siRNA formulations for cancer therapy.Methods: In this work, a novel degradable siRNA delivery system cRGD-R9-PEG-PEI-Cholesterol (rrPPC) was synthesized based on low molecular weight polyethyleneimine (PEI). Functional groups including cholesterol, cell penetrating peptides (CPPs), and poly(ethylene oxide) were introduced to PEI backbone to attain enhanced transfection efficiency and biocompatibility.Results: The synthesized rrPPC was dispersed as nanoparticles in water with an average size of 195 nm and 41.9 mV in potential. rrPPC nanoparticles could efficiently deliver siRNA into C26 clone cancer cells and trigger caveolae-mediated pathway during transmembrane transportation. By loading the signal transducer and activator of transcription 3 (STAT3) targeting siRNA, rrPPC/STAT3 siRNA (rrPPC/siSTAT3) complex demonstrated strong anti-cancer effects in multiple colon cancer models following local delivery. In addition, intravenous (IV) injection of rrPPC/siSTAT3 complex efficiently suppressed lung metastasis tumor progression with ideal in vivo safety.Conclusion: Our results provide evidence that rrPPC nanoparticles constitute a potential candidate vector for siRNA-based colon cancer gene therapy.Keywords: RNA interfering, nanoparticle, STAT3, colon cancer
format	article
author	Zhang H Men K Pan C Gao Y Li J Lei S Zhu G Li R Wei Y Duan X
author_facet	Zhang H Men K Pan C Gao Y Li J Lei S Zhu G Li R Wei Y Duan X
author_sort	Zhang H
title	Treatment of Colon Cancer by Degradable rrPPC Nano-Conjugates Delivered STAT3 siRNA
title_short	Treatment of Colon Cancer by Degradable rrPPC Nano-Conjugates Delivered STAT3 siRNA
title_full	Treatment of Colon Cancer by Degradable rrPPC Nano-Conjugates Delivered STAT3 siRNA
title_fullStr	Treatment of Colon Cancer by Degradable rrPPC Nano-Conjugates Delivered STAT3 siRNA
title_full_unstemmed	Treatment of Colon Cancer by Degradable rrPPC Nano-Conjugates Delivered STAT3 siRNA
title_sort	treatment of colon cancer by degradable rrppc nano-conjugates delivered stat3 sirna
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/9e3848211ad6468aad4d8c0fa4b36330
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Treatment of Colon Cancer by Degradable rrPPC Nano-Conjugates Delivered STAT3 siRNA

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