Shin, Ha Eun Han, Jun-Hyeok Shin, Seungyong Bae, Ga-Hyun Son, Boram Kim, Tae-Hyung Park, Hee Ho Park, Chun Gwon Park, Wooram 2024-07-18T05:30:25Z 2024-07-18T05:30:25Z 2024-07-18 2024-07 2211-3835 https://pubs.kist.re.kr/handle/201004/150252 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-L NPs 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. <feminine ordinal indicator> 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). English Elsevier BV M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles for enhanced cancer treatment through hybridization of gene therapy and cancer immunotherapy Article 10.1016/j.apsb.2024.03.004 1 Acta Pharmaceutica Sinica B, v.14, no.7, pp.3169 - 3183 Acta Pharmaceutica Sinica B 14 7 3169 3183 Y scie scopus 001265399200001 2-s2.0-85192307929 Pharmacology & Pharmacy Pharmacology & Pharmacy Article DELIVERY BCL-2 ACTIVATION ROLES STORY CELLS POLARIZATION INHIBITION INDUCTION APOPTOSIS Genetic-immunotherapy M1 macrophage-derived cellular nanovesicles Lipid nanoparticles (LNPs) Gene therapy siRNA Cancer immunotherapy Solid tumor Tumor microenvironment (TME)