用于乏氧肿瘤治疗的钌(II)基光活化化疗前药研究

doi:10.12461/PKU.DXHX202410024

大学化学 >> 2025, Vol. 40 >> Issue (7): 200-212.doi: 10.12461/PKU.DXHX202410024

用于乏氧肿瘤治疗的钌(II)基光活化化疗前药研究

王发, 陈禹, 巢晖

中山大学化学学院, 生物无机与合成化学教育部重点实验室, 广州 510006

收稿日期:2024-10-08 录用日期:2024-12-09 发布日期:2025-07-01
通讯作者: 陈禹, 巢晖 E-mail:chenyu63@mail.sysu.edu.cn;ceschh@mail.sysu.edu.cn
基金资助:
国家自然科学基金(22120102002, 22477148, 22207134)；广东省自然科学杰出青年基金(2021B1515020102)

Ruthenium(II) Complexes as Photoactivated Chemo-Prodrugs for Hypoxic Tumor Therapy

Fa Wang, Yu Chen, Hui Chao

MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510006, China

Received:2024-10-08 Accepted:2024-12-09 Published:2025-07-01
Contact: Yu Chen, Hui Chao E-mail:chenyu63@mail.sysu.edu.cn;ceschh@mail.sysu.edu.cn

摘要/Abstract

摘要： 化疗是肿瘤治疗的主要方法之一，然而化疗药物低选择性引发的毒副作用是临床面临的重大挑战。光活化治疗借助光的时空调控实现药物活性在肿瘤部位的精准调控，显著降低毒副作用。乏氧微环境是实体肿瘤的特征之一。在多种光活化治疗方案中，非氧气依赖的光活化化疗更适配乏氧肿瘤治疗。钌(II)配合物具有丰富的光物理和光化学性质，是构建光活化化疗前药的潜在候选者。钌(II)基光活化化疗前药光激发生成钌(II)水合物与游离配体，随后前者与生物大分子结合抑制其生物功能，后者通常也具有DNA损伤或蛋白抑制能力，进一步增强体系的抗肿瘤活性。钌(II)基光活化化疗前药的理性设计策略尚不明确。本文立足光活化机制，从配体配位数角度出发简要介绍钌(II)基光活化化疗前药克服乏氧肿瘤的研究进展，初步探索其分子设计策略，总结该领域面临的挑战并展望其未来应用。希望本文可以为人们继续设计出新的高效低毒钌(II)基光活化化疗前药提供参考。

关键词: 钌(II)配合物, 光活化化疗, 抗肿瘤, 乏氧

Abstract: The toxic side effects resulting from the low selectivity of chemotherapeutic drugs are a significant challenge in clinical treatment. Photoactivated therapy can achieve precise regulation of drug activity at the tumor site with the help of spatial and temporal modulation of light, which minimizes the toxic side effects. Hypoxia is a characteristic of solid tumors. Therefore, oxygen-independent photoactivated chemotherapy (PACT) matches the requirements of hypoxic tumor treatment. Due to their rich photophysical and photochemical properties, Ru(II) complexes are potential candidates for constructing PACT prodrugs. Upon irradiation, Ru(II)-based PACT prodrugs generate Ru(II)-solvent species and free ligands, which subsequently bind to biomolecules to inhibit their biological functions, and the latter usually also possess DNA-damaging or protein-inhibiting abilities, further enhancing the antitumor activity. The rational design strategy of Ru(II)-based PACT prodrugs is still unclear. Herein, we briefly introduce the research progress of Ru(II)-based PACT prodrugs to overcome hypoxic tumors from the perspective of ligand coordination number based on the photoactivation mechanism, preliminarily explore their molecular design strategies, summarize the challenges faced in this field and look forward to their future applications. We hope this review will provide a reference for the design of new efficient and low-toxic Ru(II)-based PACT prodrugs.

Key words: Ruthenium(II) complexes, Photoactivated chemotherapy, Antitumor, Hypoxia

王发, 陈禹, 巢晖. 用于乏氧肿瘤治疗的钌(II)基光活化化疗前药研究[J]. 大学化学, 2025, 40(7): 200-212.

Fa Wang, Yu Chen, Hui Chao. Ruthenium(II) Complexes as Photoactivated Chemo-Prodrugs for Hypoxic Tumor Therapy[J]. University Chemistry, 2025, 40(7): 200-212.

链接本文: https://www.dxhx.pku.edu.cn/CN/10.12461/PKU.DXHX202410024

https://www.dxhx.pku.edu.cn/CN/Y2025/V40/I7/200

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用于乏氧肿瘤治疗的钌(II)基光活化化疗前药研究

Ruthenium(II) Complexes as Photoactivated Chemo-Prodrugs for Hypoxic Tumor Therapy

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