Ionizable polymeric micelles (IPMs) for efficient siRNA delivery

Ziyu Zhou, Yu Feng, Mingzhou Jiang, Zijun Yao, Jing Wang, Feng Pan, Rulan Feng, Chong Zhao, Yinyu Ma, Jinge Zhou, Lei Sun, Xiaotian Sun, Changyou Zhan, Xiao He (), Kuan Jiang (), Jiahui Yu () and Zhiqiang Yan ()
Additional contact information
Ziyu Zhou: East China Normal University
Yu Feng: East China Normal University
Mingzhou Jiang: Huashan Hospital of Fudan University
Zijun Yao: East China Normal University
Jing Wang: East China Normal University
Feng Pan: Shanghai Fudan University
Rulan Feng: East China Normal University
Chong Zhao: East China Normal University
Yinyu Ma: Fudan University
Jinge Zhou: Kunming Medical University
Lei Sun: East China Normal University
Xiaotian Sun: Huashan Hospital of Fudan University
Changyou Zhan: Shanghai Fudan University
Xiao He: East China Normal University
Kuan Jiang: Fudan University
Jiahui Yu: East China Normal University
Zhiqiang Yan: East China Normal University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-55721-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55721-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-55721-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().