title: A Nanosystem Capable of Releasing a Photosensitizer Bioprecursor under Two-Photon Irradiation for Photodynamic Therapy.
abstract: 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.
authors: College of Materials Science and Engineering State Key Laboratory of Luminescent Materials and Devices South China University of Technology Guangzhou 510640 P.R. China.
authors: Hao
authors: H
authors: Wu
authors: College of Materials Science and Engineering State Key Laboratory of Luminescent Materials and Devices South China University of Technology Guangzhou 510640 P.R. China.
authors: Fang
authors: F
authors: Zeng
authors: Institute of Optical Communication Materials State Key Laboratory of Luminescent Materials and Devices South China University of Technology Guangzhou 510640 P.R. China.
authors: Hang
authors: H
authors: Zhang
authors: College of Materials Science and Engineering State Key Laboratory of Luminescent Materials and Devices South China University of Technology Guangzhou 510640 P.R. China.
authors: Jiangsheng
authors: J
authors: Xu
authors: Institute of Optical Communication Materials State Key Laboratory of Luminescent Materials and Devices South China University of Technology Guangzhou 510640 P.R. China.
authors: Jianrong
authors: J
authors: Qiu
authors: College of Materials Science and Engineering State Key Laboratory of Luminescent Materials and Devices South China University of Technology Guangzhou 510640 P.R. China.
authors: Shuizhu
authors: S
authors: Wu
keywords: 5‐aminolevulinic acid; mitochondrial‐targeted; photocontrolled prodrug; photodynamic therapy; two‐photon absorption