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Polymeric Nanoparticles with a Glutathione‐Sensitive Heterodimeric Multifunctional Prodrug for In Vivo Drug Monitoring and Synergistic Cancer Therapy
Author(s) -
Zhang Fuwu,
Ni Qianqian,
Jacobson Orit,
Cheng Siyuan,
Liao Arthur,
Wang Zhantong,
He Zhimei,
Yu Guocan,
Song Jibin,
Ma Ying,
Niu Gang,
Zhang Longjiang,
Zhu Guizhi,
Chen Xiaoyuan
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201801984
Subject(s) - prodrug , drug delivery , nanomedicine , glutathione , chemistry , drug , in vivo , combinatorial chemistry , conjugated system , nanotechnology , pharmacology , nanoparticle , materials science , polymer , organic chemistry , biochemistry , medicine , microbiology and biotechnology , biology , enzyme
Polymeric micelle‐based drug delivery systems have dramatically improved the delivery of small molecular drugs, yet multiple challenges remain to be overcome. A polymeric nanomedicine has now been engineered that possesses an ultrahigh loading (59 %) of a glutathione (GSH)‐sensitive heterodimeric multifunctional prodrug (HDMP) to effectively co‐deliver two synergistic drugs to tumors. An HDMP comprising of chemotherapeutic camptothecin (CPT) and photosensitizer 2‐(1‐hexyloxyethyl)‐2‐devinyl pyropheophorbide‐α (HPPH) was conjugated via a GSH‐cleavable linkage. The intrinsic fluorogenicity and label‐free radio‐chelation ( 64 Cu) of HPPH enabled direct drug monitoring by fluorescence imaging and positron emission tomography (PET). Through quantitative PET imaging, HDMP significantly improves drug delivery to tumors. The high synergistic therapeutic efficacy of HDMP‐loaded NPs highlights the rational design of HDMP, and presents exciting opportunities for polymer NP‐based drug delivery.