M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles for enhanced cancer treatment through hybridization of gene therapy and cancer immunotherapy

Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene therapy. Lipid nanoparticles (LNPs), considered a prospective vehicle for nucleic acid delivery, have demonstrated efficacy in human use during the COVID-19 pandemic. This study introduces...

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Bibliographic Details
Published in:Acta pharmaceutica Sinica. B 2024-07, Vol.14 (7), p.3169-3183
Main Authors: Shin, Ha Eun, Han, Jun-Hyeok, Shin, Seungyong, Bae, Ga-Hyun, Son, Boram, Kim, Tae-Hyung, Park, Hee Ho, Park, Chun Gwon, Park, Wooram
Format: Article
Language:English
Subjects:
Cancer immunotherapy
Gene therapy
Genetic-immunotherapy
Lipid nanoparticles (LNPs)
M1 macrophage-derived cellular nanovesicles
Original
siRNA
Solid tumor
Tumor microenvironment (TME)
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Summary:Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene therapy. Lipid nanoparticles (LNPs), considered a prospective vehicle for nucleic acid delivery, have demonstrated efficacy in human use during the COVID-19 pandemic. This study introduces a novel biomaterial-based platform, M1-polarized macrophage-derived cellular nanovesicle-coated LNPs (M1-C-LNPs), specifically engineered for a combined gene-immunotherapy approach against solid tumor. The dual-function system of M1-C-LNPs encapsulates Bcl2-targeting siRNA within LNPs and immune-modulating cytokines within M1 macrophage-derived cellular nanovesicles (M1-NVs), effectively facilitating apoptosis in cancer cells without impacting T and NK cells, which activate the intratumoral immune response to promote granule-mediating killing for solid tumor eradication. Enhanced retention within tumor was observed upon intratumoral administration of M1-C-LNPs, owing to the presence of adhesion molecules on M1-NVs, thereby contributing to superior tumor growth inhibition. These findings represent a promising strategy for the development of targeted and effective nanoparticle-based cancer genetic-immunotherapy, with significant implications for advancing biomaterial use in cancer therapeutics. M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles (M1-C-LNPs) were designed for combined gene and immunotherapy against solid tumors, with superior tumor inhibition efficacy and safety from targeted delivery and immune activation. [Display omitted]
ISSN:2211-3835
2211-3843
DOI:10.1016/j.apsb.2024.03.004