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

• Main Authors: Ha Eun Shin (Author), Jun-Hyeok Han (Author), Seungyong Shin (Author), Ga-Hyun Bae (Author), Boram Son (Author), Tae-Hyung Kim (Author), Hee Ho Park (Author), Chun Gwon Park (Author), Wooram Park (Author)
• Format: Book
• Published: Elsevier, 2024-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

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.

Item Description

2211-3835
10.1016/j.apsb.2024.03.004