Shanghai Key Laboratory of Functional Materials Chemistry , East China University of Science and Technology , 130 Meilong Road , Shanghai 200237 , P. R. China.
Biomacromolecules. 2019 Jul 8;20(7):2796-2808. doi: 10.1021/acs.biomac.9b00581. Epub 2019 Jun 19.
The development of more efficient photosensitizers with minimal damage to surrounding normal tissues has been a valuable and challenging subject during photodynamic therapy (PDT). Herein, a stimuli-activated porphyrinic photosensitizer (PEG-TPP-DNB; PEG = poly(ethylene glycol); TPP = 5,10,15,20-tetraphenylporphyrin; DNB = 2,4-dinitrobenzene) with capabilities of fluorescence and, remarkably, singlet oxygen quenching was prepared successfully for photodynamic therapy with high efficiency and biosecurity. The amphiphilic PEG-TPP-DNB could be self-assembled into nanomicelles in aqueous media and dissociated in response to reductive thiol such as glutathione. Meanwhile, the fluorescence and singlet oxygen generation of porphyrinic photosensitizer would be activated to regenerate. Moreover, the intracellular uptake and localization effectively confirmed the redox-responsive and activated behavior of PEG-TPP-DNB micelles. The cytotoxicity in vitro revealed that the micelles had low dark toxicity and great phototoxicity, and in vivo bioimaging and antitumor evaluation further indicated that the micelles possessed selective tumor imaging and targeted PDT antitumor effect as well as low systemic toxicity. Overall, this tumor microenvironment-activated photosensitizer system may provide a useful strategy for precise photodynamic therapy.
在光动力疗法（PDT）中，开发对周围正常组织损伤最小的更高效的光敏剂一直是一个有价值和具有挑战性的课题。在此，成功制备了一种具有荧光性能且具有显著单线态氧猝灭能力的刺激响应型卟啉类光敏剂（PEG-TPP-DNB；PEG = 聚乙二醇；TPP = 5,10,15,20-四苯基卟啉；DNB = 2,4-二硝基苯），用于高效和生物安全的光动力治疗。两亲性的 PEG-TPP-DNB 能够在水介质中自组装成纳米胶束，并响应还原型巯基（如谷胱甘肽）解离。同时，光敏剂的荧光和单线态氧生成会被激活而再生。此外，细胞内摄取和定位有效地证实了 PEG-TPP-DNB 胶束的氧化还原响应和激活行为。体外细胞毒性实验表明，胶束具有低暗毒性和强光毒性，体内生物成像和抗肿瘤评价进一步表明，胶束具有选择性肿瘤成像和靶向 PDT 抗肿瘤作用以及低全身毒性。总的来说，这种肿瘤微环境激活的光敏剂体系可能为精确的光动力治疗提供了一种有用的策略。
