title: Probe-inspired nano-prodrug with dual-color fluorogenic property reveals spatiotemporal drug release in living cells.
abstract: The versatility of the fluorescent probes inspires us to design fluorescently traceable prodrugs, which enables tracking the drug delivery kinetics in living cells. Herein, we constructed a self-indicating nanoprodrug with two fluorescent moieties, an aggregation-induced emission molecule (tetraphenylethylene, TPE) and a luminant anticancer drug (doxorubicin, DOX), with a pH-responsive linker between them. Except when a low pH environment is encountered, an energy-transfer relay (ETR) occurs and inactivates the fluorescence of both, showing a dark background. Otherwise, the ETR would be interrupted and evoke a dual-color fluorogenic process, giving distinct fluorogenic read out. By observing the dual-color fluorogenic scenario, we captured the kinetics of the drug release process in living cells. Because the separated TPE and DOX are both fluorescent but have a distinct spectrum, by examining the spatiotemporal pattern of TPE and DOX, we were able to precisely disclose the drug-releasing site, the releasing time, the destinations of the carriers, and the executing site of the drugs at subcellular level. Furthermore, different intracellular drug release kinetics between free doxorubicin and its nanoformulations were also observed in a real-time manner.
authors: Xiangdong
authors: X
authors: Xue
authors: Shubin
authors: S
authors: Jin
authors: Chunqiu
authors: C
authors: Zhang
authors: Keni
authors: K
authors: Yang
authors: Shuaidong
authors: S
authors: Huo
authors: Fei
authors: F
authors: Chen
authors: Guozhang
authors: G
authors: Zou
authors: Xing-Jie
authors: XJ
authors: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D002470:Cell Survival; D003116:Color; D004317:Doxorubicin / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004735:Energy Transfer; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D011355:Prodrugs; D004317:Doxorubicin
keywords: FRET; aggregation-induced emission; dual-color responsive; nanoprodrug; pH sensitive