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Multistage pH-Responsive Liposomes for Mitochondrial-Targeted Anticancer Drug Delivery

Authors

  • Ran Mo,

    1. Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, P. R. China
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  • Qiong Sun,

    1. Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, P. R. China
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  • Jingwei Xue,

    1. Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, P. R. China
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  • Nan Li,

    1. Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, P. R. China
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  • Wenyuan Li,

    1. Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia
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  • Can Zhang,

    Corresponding author
    1. Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, P. R. China
    • Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, P. R. China.
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  • Qineng Ping

    1. Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, P. R. China
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Abstract

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Zwitterionic oligopeptide liposomes (HHG2C18-L) containing a smart lipid (1,5-dioctadecyl-L-glutamyl 2-histidyl-hexahydrobenzoic acid, HHG2C18) are developed to overcome the barriers faced by anticancer drugs on the route from the site of injection into the body to the final antitumor target within transport steps with multiple physiological and biological barriers. HHG2C18-L show the multistage pH-responsive to the tumor cell (the mitochondria in this case). Their multistage pH response leads to more effective entry of the tumor cell, improved escape from the endolysosomes, and accumulation at the mitochondria (see picture).

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