Cardiolipin-Targeted NIR-II Fluorophore Causes ?Avalanche Effects? for Re-Engaging Cancer Apoptosis and Inhibiting Metastasis

文献类型： 外文期刊

第一作者： Zhang, Xiaodong

作者： Zhang, Xiaodong;Xin, Kai;Yang, Youjun;Bian, Hui;Ma, Dandan;Zhang, Xinfu;Peng, Xiaojun;Xiao, Yi;Pan, Fei

作者机构：

期刊名称：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY （ 影响因子：16.383； 五年影响因子：16.289 ）

ISSN： 0002-7863

年卷期：

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收录情况： SCI

摘要： Restoring innate apoptosis and simultaneously inhibiting metastasis by a molecular drug is an effective cancer therapeutic approach. Herein, a large rigid and V-shaped NIR-II dye, DUT850, is rationally designed for potential cardiolipin (CL) targeted chemo-phototheranostic application. DUT850 displays moderate NIR-II fluorescence, excellent photodynamic therapy (PDT) and photothermal therapy (PTT) performance, and ultrahigh photostability. More importantly, the unique rigid V-shaped backbone, positive charge, and lipophilicity of DUT850 afford its specific recognition and efficient binding to CL; such an interaction of DUT850-CL induced a spectrum of physiological disruptions, including translocation of cytochrome c, Ca2+ overload, reactive oxygen species burst, and ATP depletion, which not only activated cancer cell apoptosis but also inhibited tumor metastasis both in vitro and in vivo. Furthermore, the tight binding of DUT850-CL improves the phototoxicity of DUT850 toward cancer cells (IC50 as low as 90 nM) under safe 808 nm laser irradiation (330 mW cm-2). Upon encapsulation into bovine serum albumin (BSA), DUT850@BSA exerted a synergetic chemo-PDT-PTT effect on the 4T1 tumor mouse model, eventually leading to solid tumor annihilation and metastasis inhibition, which could be followed in real time with the NIR-II fluorescence of DUT850. This work contributed a promising approach for simultaneously re-engaging cancer cell apoptotic networks and activating the anti-metastasis pathway by targeting a pivotal upstream effector, which will bring a medical boon for inhibition of tumor proliferation and metastasis.

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