期刊
ACS NANO
卷 14, 期 1, 页码 854-866出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b07972
关键词
photodynamic therapy; aggregation-induced emission; nanoparticle; fluorescence imaging; near-infrared photosensitizer
类别
资金
- National Natural Science Foundation of China [21788102, 21525523, 21722507, 21974128, 21874121]
- Natural Science Foundation of Guangdong Province [2019B030301003]
- Science and Technology Program of Guangzhou [201804020027]
Photodynamic therapy (PDT) strategy has been widely used in tumor treatment, and the reagents for reactive oxygen species (ROS) play a crucial role. Herein, we develop a fluorogen (TTB) containing an electron-accepting benzo[1,2-b:4,5-b']dithiophene 1,1,5,5-tetraoxide core and electron-donating 4,4'-(2,2-diphenylethene-1,1-diyl)bis(N,N-diphenylaniline) groups for image-guided targeting PDT application. TTB exhibits a prominent aggregation-induced emission (AIE) property with strong near-infrared (NIR) fluorescence in aggregates and is capable of efficiently generating ROS of O-2(center dot)- and O-1(2) under white light irradiation. The nanoparticles (RGD-4R-MPD/TTB NPs) with NIR emission (similar to 730 nm), high photostability, and low dark cytotoxicity are fabricated by encapsulating TTB within polymeric matrix and then modified with RGD-4R peptide. They show excellent performance in targeting PDT treatment of PC3, HeLa, and SKOV-3 cancer cells in vitro. The investigations on pharmacokinetics, biodistribution, and long-term tracing in vivo reveal that RGD-4R-MPD/TTB NPs can selectively accumulate in tumors for real-time, long-term image-guided PDT treatment. The RGD-4R-MPD/TTB NPs-mediated PDT in multiple xenograft tumor models disclose that the growth of cervical, prostate, and ovarian cancers in mice can be effectively inhibited. These results demonstrate that the reagents employing NIR fluorogen TTB as a photosensitizer could be promising candidates for in vivo image-guided PDT treatments of tumors.
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