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Bioresponsive Chimaeric Polymersomes Mediate Sustained and Liver-Specific siRNA Transfection In Vivo

文献类型：期刊论文

作者Huang, Ri4,5; Wang, Feifei3; Fu, He2; Qi, Xinming2; Xing, Guozhen2,3; Ren, Jin2; Cheng, Liang1,4,5; Meng, Fenghua4,5; Zhong, Zhiyuan1,4,5
刊名BIOMACROMOLECULES
出版日期2023-10-23
卷号24期号:11页码:5353-5363
ISSN号1525-7797
DOI10.1021/acs.biomac.3c00813
通讯作者Ren, Jin(jren@cdser.simm.ac.cn) ; Meng, Fenghua(fhmeng@suda.edu.cn) ; Zhong, Zhiyuan(zyzhong@suda.edu.cn)
英文摘要The silencing of disease-causing genes with small interfering RNA (siRNA) offers a particularly effective therapeutic strategy for different disorders; however, its clinical efficacy relies on the development of nontoxic and tissue-specific delivery vehicles. Herein, we report that bioresponsive chimaeric polymersomes (BCP) with short poly(ethylenimine) as inner shell mediate highly efficacious, sustained, and liver-specific siRNA transfection in vivo. BCP exhibited remarkable encapsulation efficiencies of siRNA (95-100%) at siRNA-feeding contents of 15-25 wt %, to afford stable, small-sized (55-64 nm), and neutral-charged BCP-siRNA. siApoB-Loaded BCP (BCP-siApoB) outperformed lipofectamine counterparts and silenced 93% of ApoB mRNA in HepG2 cells at 50 nM siApoB without inducing cytotoxicity. Intriguingly, the in vivo studies using wild-type C57BL/6 mice revealed that BCP-siApoB preferentially accumulated in the liver, and a single dose of 4.5 mg/kg achieved over 90% downregulation of ApoB mRNA for at least 10 days. The systemic administration of BCP-siApoB at 4.5 mg/kg every 2 weeks or 1.5 mg/kg weekly in diet-induced obese mice could also achieve up to 80% silencing of ApoB mRNA. The liver specificity and silencing efficacy of BCP-siApoB could further be improved by decorating it with the trivalent N-acetylgalactosamine (TriGalNAc) ligand. These bioresponsive and liver-specific chimaeric polymersomes provide an enabling technology for siRNA therapy of various liver-related diseases.
WOS关键词MICELLAR NANOPARTICLES ; DELIVERY ; THERAPY ; CANCER ; RNA ; PKA
资助项目National Natural Science Foundation of China[NSFC 52033006] ; National Natural Science Foundation of China[52233007]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry ; Polymer Science
语种英语
WOS记录号WOS:001104905500001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/308167]  
专题新药研究国家重点实验室
通讯作者Ren, Jin; Meng, Fenghua; Zhong, Zhiyuan
作者单位1.Soochow Univ, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210023, Peoples R China
4.Soochow Univ, State Key Lab Radiat Med & Protect, Suzhou 215123, Peoples R China
5.Soochow Univ, Coll Chem Chem Engn & Mat Sci, Biomed Polymers Lab, Suzhou 215123, Peoples R China
推荐引用方式
GB/T 7714		 Huang, Ri,Wang, Feifei,Fu, He,et al. Bioresponsive Chimaeric Polymersomes Mediate Sustained and Liver-Specific siRNA Transfection In Vivo[J]. BIOMACROMOLECULES,2023,24(11):5353-5363.
APA Huang, Ri.,Wang, Feifei.,Fu, He.,Qi, Xinming.,Xing, Guozhen.,...&Zhong, Zhiyuan.(2023).Bioresponsive Chimaeric Polymersomes Mediate Sustained and Liver-Specific siRNA Transfection In Vivo.BIOMACROMOLECULES,24(11),5353-5363.
MLA Huang, Ri,et al."Bioresponsive Chimaeric Polymersomes Mediate Sustained and Liver-Specific siRNA Transfection In Vivo".BIOMACROMOLECULES 24.11(2023):5353-5363.

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来源：上海药物研究所

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