Polymeric micelleplexes for improved photothermal endosomal escape and delivery of siRNA

Gang Chen; Ling Ding; Pengkai Wu; Yiwen Zhou; Minjie Sun; Kaikai Wang; David Oupický

doi:10.1002/pat.4372

Polymeric micelleplexes for improved photothermal endosomal escape and delivery of siRNA

Gang Chen, Ling Ding, Pengkai Wu, Yiwen Zhou, Minjie Sun, Kaikai Wang, David Oupický

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Effective endosomal escape is required for practical application of nucleic acid therapeutics. In this study, we prepared siRNA micelleplexes with photothermally triggered endosomal escape and improved gene silencing activity in vitro. The micelleplexes were prepared from cholesterol-modified and CXCR4-inhibiting poly(amido amine)s (PAMD-Ch). Near-infrared dye IR780 was encapsulated in cationic PMAD-Ch micelles, which then were used to form IR780 micelleplexes with siRNA. The micelleplexes displayed improved gene silencing efficiency upon laser irradiation, which was attributed to enhanced endosomal escape because of the photothermal effects of the encapsulated IR780. The IR780 micelleplexes retained the CXCR4 antagonism and inhibition of cancer cell invasion of the parent PAMD. Overall, this study validates codelivery of IR780 in siRNA micelleplexes as promising photothermally controlled siRNA delivery approach.

Original language	English (US)
Pages (from-to)	2593-2600
Number of pages	8
Journal	Polymers for Advanced Technologies
Volume	29
Issue number	10
DOIs	https://doi.org/10.1002/pat.4372
State	Published - Oct 2018

Keywords

IR780
endosomal escape
photothermal
polyplex
siRNA delivery

ASJC Scopus subject areas

Polymers and Plastics

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10.1002/pat.4372

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title = "Polymeric micelleplexes for improved photothermal endosomal escape and delivery of siRNA",

abstract = "Effective endosomal escape is required for practical application of nucleic acid therapeutics. In this study, we prepared siRNA micelleplexes with photothermally triggered endosomal escape and improved gene silencing activity in vitro. The micelleplexes were prepared from cholesterol-modified and CXCR4-inhibiting poly(amido amine)s (PAMD-Ch). Near-infrared dye IR780 was encapsulated in cationic PMAD-Ch micelles, which then were used to form IR780 micelleplexes with siRNA. The micelleplexes displayed improved gene silencing efficiency upon laser irradiation, which was attributed to enhanced endosomal escape because of the photothermal effects of the encapsulated IR780. The IR780 micelleplexes retained the CXCR4 antagonism and inhibition of cancer cell invasion of the parent PAMD. Overall, this study validates codelivery of IR780 in siRNA micelleplexes as promising photothermally controlled siRNA delivery approach.",

keywords = "IR780, endosomal escape, photothermal, polyplex, siRNA delivery",

author = "Gang Chen and Ling Ding and Pengkai Wu and Yiwen Zhou and Minjie Sun and Kaikai Wang and David Oupick{\'y}",

note = "Funding Information: National Natural Science Foundation of China, Grant/Award Numbers: 81573377 and 81373983; China Postdoctoral Science Foundation, Grant/Award Number: 2016M601923; Postgraduate Research & Practice Innovation Program of Jiangsu Province, Grant/Award Number: KYCX17_0671; Changjiang Scholar Program; National Science and Technology Major Project, Grant/Award Number: 2017YFA0205400 Funding Information: This work was financially supported by the National Science and Technology Major Project (2017YFA0205400), the Changjiang Scholar Program, the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX17_0671), the China National Science Foundation (No. 81373983, 81573377), and the China Postdoctoral Science Foundation (No. 2016M601923). Publisher Copyright: {\textcopyright} 2018 John Wiley & Sons, Ltd.",

year = "2018",

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doi = "10.1002/pat.4372",

language = "English (US)",

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AU - Chen, Gang

AU - Ding, Ling

AU - Wu, Pengkai

AU - Zhou, Yiwen

AU - Sun, Minjie

AU - Wang, Kaikai

AU - Oupický, David

N1 - Funding Information: National Natural Science Foundation of China, Grant/Award Numbers: 81573377 and 81373983; China Postdoctoral Science Foundation, Grant/Award Number: 2016M601923; Postgraduate Research & Practice Innovation Program of Jiangsu Province, Grant/Award Number: KYCX17_0671; Changjiang Scholar Program; National Science and Technology Major Project, Grant/Award Number: 2017YFA0205400 Funding Information: This work was financially supported by the National Science and Technology Major Project (2017YFA0205400), the Changjiang Scholar Program, the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX17_0671), the China National Science Foundation (No. 81373983, 81573377), and the China Postdoctoral Science Foundation (No. 2016M601923). Publisher Copyright: © 2018 John Wiley & Sons, Ltd.

PY - 2018/10

Y1 - 2018/10

N2 - Effective endosomal escape is required for practical application of nucleic acid therapeutics. In this study, we prepared siRNA micelleplexes with photothermally triggered endosomal escape and improved gene silencing activity in vitro. The micelleplexes were prepared from cholesterol-modified and CXCR4-inhibiting poly(amido amine)s (PAMD-Ch). Near-infrared dye IR780 was encapsulated in cationic PMAD-Ch micelles, which then were used to form IR780 micelleplexes with siRNA. The micelleplexes displayed improved gene silencing efficiency upon laser irradiation, which was attributed to enhanced endosomal escape because of the photothermal effects of the encapsulated IR780. The IR780 micelleplexes retained the CXCR4 antagonism and inhibition of cancer cell invasion of the parent PAMD. Overall, this study validates codelivery of IR780 in siRNA micelleplexes as promising photothermally controlled siRNA delivery approach.

AB - Effective endosomal escape is required for practical application of nucleic acid therapeutics. In this study, we prepared siRNA micelleplexes with photothermally triggered endosomal escape and improved gene silencing activity in vitro. The micelleplexes were prepared from cholesterol-modified and CXCR4-inhibiting poly(amido amine)s (PAMD-Ch). Near-infrared dye IR780 was encapsulated in cationic PMAD-Ch micelles, which then were used to form IR780 micelleplexes with siRNA. The micelleplexes displayed improved gene silencing efficiency upon laser irradiation, which was attributed to enhanced endosomal escape because of the photothermal effects of the encapsulated IR780. The IR780 micelleplexes retained the CXCR4 antagonism and inhibition of cancer cell invasion of the parent PAMD. Overall, this study validates codelivery of IR780 in siRNA micelleplexes as promising photothermally controlled siRNA delivery approach.

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Polymeric micelleplexes for improved photothermal endosomal escape and delivery of siRNA

Abstract

Keywords

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