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

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

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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 tu-mor.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 in-tratumoral 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 pres-ence 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.

Genetic-immunotherapyM1 macrophage-derived cellular nanovesiclesLipid nanoparticles(LNPs)Gene therapysiRNACancer immunotherapySolid tumorTumor microenvironment(TME)

Ha Eun Shin、Jun-Hyeok Han、Seungyong Shin、Ga-Hyun Bae、Boram Son、Tae-Hyung Kim、Hee Ho Park、Chun Gwon Park、Wooram Park

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

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

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

Department of Bioengineering,Hanyang University,Seoul 04763,Republic of Korea

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

Department of Biomedical Engineering,SKKU,Suwon,Gyeonggi 16419,Republic of Korea

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

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Basic Science Research Program grant through the National Research Foundation of Korea(NRF)of the Republic of KoreaBasic Science Research Program grant through the National Research Foundation of Korea(NRF)of the Republic of KoreaBasic Science Research Program grant through the National Research Foundation of Korea(NRF)of the Republic of KoreaBasic Science Research Program grant through the National Research Foundation of Korea(NRF)of the Republic of KoreaMinistry of Science and ICT(MSIT)of the Republic of Korea,a grant of the Korea Health Technology R&D Project through the KorMinistry of Health & Welfare,Republic of KoreaKIST Institutional Program of the Republic of Korea

2021R1A2C4001776RS-2023-00218648RS-2023-002424432023-00208913RS-2023-002660152E32351-23-130

2024

10.1016/j.apsb.2024.03.004

药学学报(英文版)

药学学报(英文版)

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ISSN：
年,卷(期)：2024.14(7)