期刊论文详细信息
Drug Delivery
Dual-ligand modified liposomes provide effective local targeted delivery of lung-cancer drug by antibody and tumor lineage-homing cell-penetrating peptide
Jinjin Wang1  Ge Lin2  Deependra Tyagi3  Congcong Lin3  Hubiao Chen3  Ge Zhang3  Xue Zhang3  Zhaoxiang Bian3  Muhammad Kashif Riaz3  Aiping Lu4  Zhijun Yang4  Yanbo Zhang5 
[1] Changshu Research Institute, Hong Kong Baptist University, Changshu Economic and Technological Development (CETD) Zone, Changshu, Chin;School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China;School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China;School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China;Changshu Research Institute, Hong Kong Baptist University, Changshu Economic and Technological Development (CETD) Zone, Changshu, Chin;School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;
关键词: Dual-ligand liposomes;    carbonic anhydrase IX;    tumor lineage-homing cell penetrating peptide;    pulmonary delivery;    orthotopic lung cancer model;   
DOI  :  10.1080/10717544.2018.1425777
来源: publisher
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【 摘 要 】

The abilities of a drug delivery system to target and penetrate tumor masses are key factors in determining the system’s chemotherapeutic efficacy. Here, we explored the utility of an anti-carbonic anhydrase IX (anti-CA IX) antibody and CPP33 dual-ligand modified triptolide-loaded liposomes (dl-TPL-lip) to simultaneously enhance the tumor-specific targeting and increase tumor cell penetration of TPL. In vitro, the dl-TPL-lip increased the cytotoxicity of TPL in CA IX-positive lung cancer cells, which showed tunable size (137.6 ± 0.8 nm), high-encapsulation efficiency (86.3 ± 2.6%) and sustained release. Dl-TPL-lip significantly improved the ability of liposomes to penetrate 3 D tumor spheroids and exhibited a superior inhibiting effect. Furthermore, pharmacokinetic studies in rats that received TPL liposomal formulations by endotracheal administration showed a reduced concentration of TPL (17.3%–30.6% compared to free TPL) in systemic circulation. After pulmonary administration in orthotopic lung tumor-bearing mice, dl-TPL-lip significantly enhanced TPL anti-cancer efficacy without apparent systemic toxicity. This dual-ligand modified liposomal vehicle presents a potential system for localized and targeted delivery of anti-cancer drugs to improve their efficacy.

【 授权许可】

CC BY   

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