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Ionizable polymeric micelles (IPMs) for efficient siRNA delivery

ABSTRACT: Lipid nanoparticles (LNPs) are widely used for nucleic acid delivery but face challenges like limited targeting and accelerated blood clearance. We design three ionizable oligo-mers (IOs) that, with PLA-PEG, form Ionizable Polymeric Micelles (IPMs), a potential siRNA delivery system, which can achieve lysosomal escape. FAPi-modified IPMs (FAPi-IPMs) show higher targeting of activated hepatic stellate cells (HSCs) compared to hepatocytes, silencing both HSP47 and HMGB1, reducing collagen secretion and liv-er inflammation, effectively treating fibrosis. Moreover, IPMs and FAPi-IPMs mitigate accelerated blood clearance and produce fewer PEG antibodies than LNPs. Unlike LNPs, which adsorb apolipoprotein E (ApoE), IPMs and FAPi-IPMs show minimal apolipoprotein adsorption, differentiating their targeting effects from LNPs. In conclu-sion, IPMs represent an alternative nucleic acid delivery system with superior targeting and reduced immune clearance.

INSTRUMENT(S): maXis

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Serum

SUBMITTER: Ziyu Zhou

LAB HEAD: Zhiqiang Yan

PROVIDER: PXD057444 | Pride | 2024-11-21

REPOSITORIES: Pride

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			Action	DRS
	FAPi-IPM_S1-A7_1_5901.d.zip	Other
	IPM_S1-A5_1_5899.d.zip	Other
	LNP_S1-A6_1_5900.d.zip	Other
	Protein-Experiment-Setting-JTJD.txt	Txt
	checksum.txt	Txt

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