Promoting DNA alkylation of hypoxia-activated molecular prodrug for cooperative precision photodynamic-chemotherapy

IF 3.9 3区工程技术 Q2 CHEMISTRY, APPLIED

Dyes and Pigments Pub Date : 2026-05-01 Epub Date: 2025-12-29 DOI:10.1016/j.dyepig.2025.113532

Yang Zou , Xinmeng Yu , Manqing Wu , Shuang E , Yang Xuan , Yinan Zhao , Jiangli Fan , Shubiao Zhang

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Abstract

The combination of photodynamic therapy (PDT) and chemotherapy is a promising strategy to improve the effect of tumor treatment. However, the existing construction systems have insufficient killing selectivity and unclear synergistic mechanism. Herein, we developed a novel anticancer strategy based on a hypoxia-activated molecular prodrug (Cy-NM), which was formed by the covalent connection of an alkylating agent (NM) and a photodynamic photosensitizer (Cy-NH₂), to achieve cooperative precision photodynamic-chemotherapy. Cy-NM with positive charge could structure-inherent targeting (SIT) to tumors and localized to the mitochondria of cancer cells. Under the action of azo reductase, Cy-NM was converted into Cy-NH₂, thereby enhancing the photodynamic effect through the intramolecular charge transfer (ICT) effect and releasing NM. PDT consumed oxygen to further exacerbate tumor hypoxia and promote drug release, while the released drugs enhanced the photodynamic damage to mitochondria. The two treatments exhibited a synergistic promotion effect, achieving more effective and selective in killing cancer cells. Moreover, the fluorescence of Cy-NM changed from “off” to “on” after activation, which realized precise fluorescence diagnosis and visual treatment of tumors. Therefore, this prodrug design strategy offers a new perspective for improving the accuracy and efficiency of tumor treatment.

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促进缺氧激活分子前体药物DNA烷基化的协同精确光动力化疗

光动力疗法（PDT）与化疗相结合是提高肿瘤治疗效果的一种有前景的策略。然而，现有的构建体系杀灭选择性不足，协同机制不明确。在此，我们开发了一种新的基于缺氧激活的分子前药（Cy-NM）的抗癌策略，该策略是由烷基化剂（NM）和光动力光敏剂（Cy-NH2）的共价连接形成的，以实现协同精确光动力化疗。带正电荷的Cy-NM具有结构固有靶向肿瘤的功能，定位于癌细胞的线粒体。在偶氮还原酶的作用下，Cy-NM被转化为Cy-NH2，从而通过分子内电荷转移（ICT）效应增强光动力效应，释放NM。PDT消耗氧气，进一步加剧肿瘤缺氧，促进药物释放，而释放的药物则增强了对线粒体的光动力损伤。两种治疗方法表现出协同促进作用，对癌细胞的杀伤更有效、选择性更强。并且Cy-NM激活后荧光由“灭”变为“亮”，实现了肿瘤的精确荧光诊断和视觉治疗。因此，这种前药设计策略为提高肿瘤治疗的准确性和效率提供了新的视角。

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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.