Iron Oxide Nanoparticle-Mediated mRNA Delivery to Hard-to-Transfect Cancer Cells.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101534003 Publication Model: Electronic Cited Medium: Print ISSN: 1999-4923 (Print) Linking ISSN: 19994923 NLM ISO Abbreviation: Pharmaceutics Subsets: PubMed not MEDLINE

Original Publication: Basel, Switzerland : MDPI

mRNA-based therapeutics have emerged as a promising strategy for cancer treatment. However, the effective delivery of mRNA into hard-to-transfect cancer cells remains a significant challenge. This study introduces a novel approach that utilizes iron oxide nanoparticles (NPs) synthesized through a layer-by-layer (LbL) method for safe and efficient mRNA delivery. The developed NPs consist of an iron oxide core modified with a thin charge-bearing layer, an mRNA middle layer, and an outer layer composed of perfluorinated polyethyleneimine with heparin (PPH), which facilitates efficient mRNA delivery. Through a comparative analysis of four nanoparticle delivery formulations, we investigated the effects of the iron oxide core's surface chemistry and surface charge on mRNA complexation, cellular uptake, and mRNA release. We identified an optimal and effective mRNA delivery platform, namely, (IOCCP)-mRNA-PPH, capable of transporting mRNA into various hard-to-transfect cancer cell lines in vitro. The (IOCCP)-mRNA-PPH formulation demonstrated significant enhancements in cellular internalization of mRNA, facilitated endosomal escape, enabled easy mRNA release, and exhibited minimal cytotoxicity. These findings suggest that (IOCCP)-mRNA-PPH holds great promise as a solution for mRNA therapy against hard-to-transfect cancers.

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R01EB026890 United States NH NIH HHS

Keywords: cancer; iron oxide nanoparticle; layer-by-layer; mRNA delivery; mRNA therapy

Date Created: 20230729 Latest Revision: 20230801

20230801

PMC10384052

10.3390/pharmaceutics15071946

37514132