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Nanomized tumor-microenvironment-active NIR fluorescent prodrug for ensuring synchronous occurrences of drug release and fluorescence tracing

Li, Qiang, Cao, Jun, Wang, Qi, Zhang, Jie, Zhu, Shiqin, Guo, Zhiqian, Zhu, Wei-Hong
Journal of materials chemistry B 2019 v.7 no.9 pp. 1503-1509
active ingredients, adverse effects, antineoplastic agents, bioavailability, biocompatibility, fluorescence, glutathione, lung neoplasms, metabolism, monitoring, near-infrared spectroscopy, neoplasm cells, photostability, polymers, therapeutics, tissues
Improving the bioavailability and tumor-targeting ability of a prodrug, as well as monitoring its active ingredient release in vivo, is still a challenge in cancer diagnosis and therapy. Herein, a specific nanomized tumor-microenvironment-active near-infrared (NIR) fluorescent DCM-S-GEM/PEG prodrug was developed as a potent monitoring platform, wherein we conjugated antitumor drug gemcitabine (GEM) and NIR fluorescent chromophore dicyanomethylene-4H-pyran (DCM) via glutathione (GSH)-activatable disulfide linker and encapsulated DCM-S-GEM into an amphiphilic polymer DSPE-mPEG by self-assembly. The nanomized DCM-S-GEM/PEG prodrug exhibits excellent photostability and high biocompatibility, significantly improving the therapeutic efficacy toward lung tumor cells with fewer side-effects toward normal cells. Furthermore, when compared with the standalone DCM-S-GEM prodrug, the micellization with diblock DSPE-mPEG avoids fast metabolism, facilitates the accumulation of drugs in lung tumor tissues, displays longer tumor retention, and realizes precise drug release in lung tumors. The nanomized DCM-S-GEM/PEG prodrug can be developed as a promising tool to monitor prodrug delivery and activation processes in vivo.