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Light-Activatable Prodrug and AIEgen Copolymer Nanoparticle for Dual-Drug Monitoring and Combination Therapy

2019; American Chemical Society; Volume: 11; Issue: 20 Linguagem: Inglês

10.1021/acsami.9b02346

1944-8252

Peng Wu, Xuefeng Wang, Zigui Wang, Wen Ma, Jinshan Guo, Jianjun Chen, Zhiqiang Yu, Jizhen Li, Dongfang Zhou,

Advanced biosensing and bioanalysis techniques

Polyprodrug nanoparticles have been employed recently for safer and more effective cancer treatment. However, it remains a challenge to elucidate how and when the polyprodrug nanoparticles are dissociated and activated to release active drugs in cancer cells. Herein, a visible light-activatable Pt(IV) prodrug and an aggregation-induced emission luminogen (AIEgen) were copolymerized and embedded in the main chain of PtAIECP, and the chemotherapeutic doxorubicin (DOX) was subsequently encapsulated in the nanoparticles self-assembled by PtAIECP (PtAIECP@DOX NP). PtAIECP@DOX NP enabled the monitoring of both the light-activation of Pt(IV) prodrug to active Pt(II) and release of encapsulated DOX intracellularly through the fluorescence "turn-on" in the course of visible-light-induced polymer-main-chain cleavage and self-assembled structure dissociation in vitro and ex vivo. The synergistic anticancer efficacy of the activated Pt(II) drug and DOX in PtAIECP@DOX NP was also investigated in vitro and in vivo. The implementation of polyprodrug and AIE combination strategy empowered dual drug release and monitoring, which could be further used to guide the temporal and spatial control of light irradiation to maximize therapeutic efficiency, and will inspire other combinational bioimaging and therapy strategies.