From cell membrane to lysosome: Arginine modification boosts the phototoxic index of zinc phthalocyanine for efficient bladder cancer treatment

IF 4.2 3区工程技术 Q2 CHEMISTRY, APPLIED

Dyes and Pigments Pub Date : 2025-09-05 DOI:10.1016/j.dyepig.2025.113219

Xinlu Bao , Kebin Ye , Zhikang Song , Mingzhu Zhang, Shaohua Wei, Lin Zhou

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Abstract

Photodynamic therapy (PDT) utilizes reactive oxygen species (ROS) generated by photosensitizers under light to kill cancer cells. The phototoxic index (PI) indicates the safe therapeutic window of photosensitizers, and an ideal photosensitizer should have a high PI. Monosubstituted zinc phthalocyanine (ZnPc-COOH) exhibits excellent phototoxicity in bladder cancer cell (T24, IC₅₀ = 10.7 nM). However, its localization in mitochondria leads to high dark toxicity (IC₅₀ = 2.12 μM), resulting in a PI of less than 200. In this study, the binding ability of phthalocyanine to the cell membrane was significantly enhanced by side-chain modification with arginine. By taking advantage of the fluidity of the membrane structure, the drug was transported to the lysosome. After modification with Arg, the dark toxicity of ZnPc-COOH decreased by nearly 100 times, and the PI increased to 8979, which is 12 times that of the clinical photosensitizer Photosens®. In a mouse model of non-muscle-invasive bladder cancer (NMIBC), ZnPc-Arg demonstrated therapeutic effects comparable to those of the clinical drug mitomycin C (MMC). This study provides valuable references for the design of photosensitizers with high PI.

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从细胞膜到溶酶体：精氨酸修饰提高酞菁锌的光毒性指数，有效治疗膀胱癌

光动力疗法（PDT）利用光敏剂在光线下产生的活性氧（ROS）杀死癌细胞。光毒性指数（PI）表示光敏剂的安全治疗窗口，理想的光敏剂应具有较高的PI。单取代酞菁锌（ZnPc-COOH）对膀胱癌细胞具有良好的光毒性（T24, IC50 = 10.7 nM）。然而，由于其定位于线粒体，导致高暗毒性（IC50 = 2.12 μM），导致PI小于200。在本研究中，通过精氨酸侧链修饰，酞菁与细胞膜的结合能力显著增强。利用膜结构的流动性，将药物输送到溶酶体中。经精氨酸修饰后，ZnPc-COOH的暗毒性降低了近100倍，PI提高到8979，是临床光敏剂Photosens®的12倍。在非肌肉侵袭性膀胱癌（NMIBC）小鼠模型中，ZnPc-Arg显示出与临床药物丝裂霉素C （MMC）相当的治疗效果。本研究为高PI光敏剂的设计提供了有价值的参考。

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来源期刊

Dyes and Pigments 工程技术-材料科学：纺织

CiteScore

8.20

自引率

13.30%

发文量

933

审稿时长

33 days

期刊介绍： Dyes and Pigments covers the scientific and technical aspects of the chemistry and physics of dyes, pigments and their intermediates. Emphasis is placed on the properties of the colouring matters themselves rather than on their applications or the system in which they may be applied. Thus the journal accepts research and review papers on the synthesis of dyes, pigments and intermediates, their physical or chemical properties, e.g. spectroscopic, surface, solution or solid state characteristics, the physical aspects of their preparation, e.g. precipitation, nucleation and growth, crystal formation, liquid crystalline characteristics, their photochemical, ecological or biological properties and the relationship between colour and chemical constitution. However, papers are considered which deal with the more fundamental aspects of colourant application and of the interactions of colourants with substrates or media. The journal will interest a wide variety of workers in a range of disciplines whose work involves dyes, pigments and their intermediates, and provides a platform for investigators with common interests but diverse fields of activity such as cosmetics, reprographics, dye and pigment synthesis, medical research, polymers, etc.