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성균관대학교, 현 하와이주립대

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Acta Pharm. Sin. B, Available online 7 March 2024 | https://doi.org/10.1016/j.apsb.2024.03.004 M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles for enhanced cancer treatment through hybridization of gene therapy and cancer immunotherapy

Ha Eun Shin ^a, Jun-Hyeok Han ^a,b, Seungyong Shin ^a, Ga-Hyun Bae^a,c, Boram Son ^d, Tae-Hyung Kim ^e, Hee Ho Park ^d, Chun Gwon Park ^b,f,g, Wooram Park^a,c,g

^aDepartment of Integrative Biotechnology, Sungkyunkwan University (SKKU), Suwon, Gyeonggi 16419, Republic of Korea

^bDeparment of Inteligent Precision Healthcare Convergence, SKKU, Suwon, Gyeonggi 16419, Republic of Korea

^cDepartment of MetaBioHealth, SKKU Institute for Convergence, SKKU, Suwon, Gyeonggi 16419, Republic of Korea

^dDepartment of Bioengineering, Hanyang University, Seoul 04763, Republic of Korea

^eDepartment of Integrative Engineering, Chung-Ang University, Seoul 06974, Republic of Korea

^fDepartment of Biomedical Engineering, SKKU, Suwon, Gyeonggi 16419, Republic of Korea

^gKorea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea

Corresponding authors: Chun Gwon Park, Wooram Park

Abstract

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.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-04-16)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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