hybrid-targeting nanoparticle for penetrable delivery of temozolomide to enhance glioblastoma therapy
hemotherapy for glioblastoma (GBM) has not achieved the desired outcome due to inefficient bloodbrain barrier (BBB) penetration and limited tumor-specific drug accumulation. Strategies that employ bioinspired nanoparticles to enhance targeted drug accumulation can help improve therapeutic efficacy. In this work, a novel nanoparticle, PCM@TMA-lip, exhibiting hybrid-targeting capabilities, is presented, with an engineered cell membrane coated on a lipid core. The membrane modified with a biologically derived peptide enables PCM@TMA-lip to evade immune clearance and enable precise tumor targeting. The lipid core with docosahexaenoic acid (DHA)-conjugated temozolomide (TMZ) enhances FABP7-mediated uptake, promotes lysosomal escape via lipid peroxidation, and reduces tumor migration and drug resistance. In vitro, PCM@TMA-lip inhibited tumor cell malignancy and suppressed the growth of 3D spheroids. In vivo, it suppressed tumorprogression, reduced Ki67+ proliferation, increased TUNEL+ apoptosis, and prolonged survival in GBM-bearing mice, highlighting its potential as an effective strategy to improve GBM chemotherapy.
Wang, Guanru、Wang, Ying、Jin, Zengcai、Zhou, Jing、He, Jun、Li, Yaping、Guo, Hao、Wei, Mengxin
National Advanced Medical Engineering Research Center, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Shanghai 201203, PR China;State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR ChinaDepartment of Oncology, Shanxi Province Academy of Traditional Chinese Medicine, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan 030012, PR ChinaDepartment of Oncology, Shanxi Province Academy of Traditional Chinese Medicine, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan 030012, PR ChinaDepartment of Oncology, Shanxi Province Academy of Traditional Chinese Medicine, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan 030012, PR ChinaNational Advanced Medical Engineering Research Center, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Shanghai 201203, PR ChinaState Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China;Department of Anesthesiology, Shanxi Provincial People’s Hospital, Taiyuan 030000, PR China;Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica, Shandong 264000, PR China;Shandong Laboratory of Yantai Drug Discovery, Bohai rim Advanced Research Institute for Drug Discovery, Yantai 264117, PR ChinaDepartment of Anesthesiology, Shanxi Provincial People’s Hospital, Taiyuan 030000, PR ChinaSchool of Chinese Materia Medical Nanjing University of Chinese Medicine, Nanjing 210023, PR China
肿瘤学药学
Glioblastomahemotherapyrug deliveryumor-specific drug accumulationumor-suppressive effects
Glioblastomahemotherapyrug deliveryumor-specific drug accumulationumor-suppressive effects
Wang, Guanru,Wang, Ying,Jin, Zengcai,Zhou, Jing,He, Jun,Li, Yaping,Guo, Hao,Wei, Mengxin.hybrid-targeting nanoparticle for penetrable delivery of temozolomide to enhance glioblastoma therapy[EB/OL].(2025-07-28)[2025-08-31].https://chinaxiv.org/abs/202507.00454.点此复制
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