CELL INTELLIGENCE · 肿瘤细胞治疗研究

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.