A Nanosystem Capable of Releasing a Photosensitizer Bioprecursor under Two-Photon Irradiation for Photodynamic Therapy.
A Nanosystem Capable of Releasing a Photosensitizer Bioprecursor under Two-Photon Irradiation for Photodynamic Therapy.
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DOI：
10.1002/advs.201500254
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发表时间：
2016-02
期刊：
影响因子：
15.1
通讯作者：
Wu, Shuizhu
中科院分区：
文献类型：
--
作者：
Wu, Hao;Zeng, Fang;Zhang, Hang;Xu, Jiangsheng;Qiu, Jianrong;Wu, Shuizhu
The applications of photodynamic therapy (PDT) are usually limited by photosensitizers' side effects and singlet oxygen's short half‐life. Herein, a mitochondria‐targeted nanosystem is demonstrated to enhance the PDT efficacy by releasing a bio‐precursor of photosensitizer under two‐photon irradiation. A phototriggerable coumarin derivative is first synthesized by linking 5‐aminolevulinic acid (5‐ALA, the bio‐precursor) to coumarin; and the nanosystem (CD‐ALA‐TPP) is then fabricated by covalently incorporating this coumarin derivative and a mitochondria‐targeting compound triphenylphosphonium (TPP) onto carbon dots (CDs). Upon cellular internalization, the nanosystem preferentially accumulates in mitochondria; and under one‐ or two‐photon irradiation, it releases 5‐ALA molecules that are then metabolized into protoporphyrin IX in mitochondria through a series of biosynthesis processes. The subsequent red light irradiation induces this endogenously synthesized photosensitizer to generate singlet oxygen, thereby causing oxidant damage to mitochondria and then the apoptosis of the cells. Analysis via 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyltetrazolium bromide (MTT) assays indicate that the novel PDT system exhibits enhanced cytotoxicity toward cancer cells. This study may offer a new strategy for designing PDT systems with high efficacy and low side effects.
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