Ionizable polymeric micelles (IPMs) for efficient siRNA delivery

被引：6

作者：

Zhou, Ziyu ^{[1
,2
]}

Feng, Yu ^{[1
]}

Jiang, Mingzhou ^{[3
]}

Yao, Zijun ^{[1
]}

Wang, Jing ^{[1
]}

Pan, Feng ^{[4
,5
]}

Feng, Rulan ^{[1
]}

Zhao, Chong ^{[1
]}

Ma, Yinyu ^{[6
,7
]}

Zhou, Jinge ^{[8
]}

Sun, Lei ^{[1
,9
]}

Sun, Xiaotian ^{[3
]}

Zhan, Changyou ^{[4
,5
,6
,7
]}

He, Xiao ^{[1
,10
]}

Jiang, Kuan ^{[6
,7
,11
,12
]}

Yu, Jiahui ^{[1
]}

Yan, Zhiqiang ^{[1
,10
]}

机构：

[1] East China Normal Univ, Inst Biomed Engn & Technol, Shanghai Engn Res Ctr Mol Therapeut & New Drug Dev, Sch Chem & Mol Engn, Shanghai, Peoples R China

[2] East China Normal Univ, Sch Pharm, Shanghai, Peoples R China

[3] Fudan Univ, HuaShan Hosp, Dept Cardiothorac Surg, Shanghai, Peoples R China

[4] Shanghai Fudan Univ, Sch Pharm, Key Lab Smart Drug Delivery, Minist Educ, Shanghai, Peoples R China

[5] Shanghai Fudan Univ, Sch Pharm, Dept Pharm, Key Lab Smart Drug Delivery, Shanghai, Peoples R China

[6] Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai, Peoples R China

[7] Fudan Univ, State Key Lab Mol Engn Polymers, Shanghai, Peoples R China

[8] Kunming Med Univ, Inst Biomed Engn, Kunming, Peoples R China

[9] Univ Calif San Diego, Dept Nanoengn, Chem Engn Program, La Jolla, CA USA

[10] East China Normal Univ, Shanghai Frontiers Sci Ctr Mol Intelligent Synth, Sch Chem & Mol Engn, Shanghai, Peoples R China

[11] Fudan Univ, Eye & ENT Hosp, Eye Inst, Shanghai, Peoples R China

[12] Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol, Shanghai, Peoples R China

来源：

NATURE COMMUNICATIONS | 2025年 / 16卷 / 01期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

LIPID NANOPARTICLES; MULTICENTER; PACLITAXEL; HSC;

D O I：

10.1038/s41467-024-55721-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Lipid nanoparticles (LNPs) are widely used for nucleic acid delivery but face challenges like limited targeting and accelerated blood clearance (ABC) effect. We design three ionizable oligomers (IOs) that, with polylactide-polyethylene glycol (PLA-PEG), form a potential siRNA delivery system, named Ionizable Polymeric Micelles (IPMs). The siRNA encapsulated IPMs escape from lysosomes upon cellular uptake, and silence the target gene. A fibroblast activation protein inhibitor modified IPMs (FAPi-IPMs) show higher targeting for activated hepatic stellate cells (HSCs) compared to that for hepatocytes, silencing both HSP47 and HMGB1, reducing collagen secretion and liver inflammation, thereby treating fibrosis. Moreover, IPMs and FAPi-IPMs mitigate ABC effect and produce fewer PEG antibodies than LNPs, and show minimal apolipoprotein adsorption in vivo compared with LNPs, differentiating their targeting effects from LNPs. In conclusion, IPMs represent a nucleic acid delivery system with alternative targeting ability and reduced ABC effect.

引用

页数：15

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