Wang Jun, Liu Yina, Cui Tingting, Yang Huanghao, Lin Lisen
New Cornerstone Science Laboratory, MOE Key Laboratory for Analytical Science of Food Safety and Biology, Engineering Technology Research Center on Reagent and Instrument for Rapid Detection of Product Quality and Food Safety in Fujian Province, College of Chemistry, Fuzhou University Fuzhou 350108 China
Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore Singapore 119074 Singapore.
Chem Sci. 2024 Jun 7;15(26):9915-9926. doi: 10.1039/d4sc02129k. eCollection 2024 Jul 3.
Chemodynamic therapy (CDT) is a potential cancer treatment strategy, which relies on Fenton chemistry to transform hydrogen peroxide (HO) into highly cytotoxic reactive oxygen species (ROS) for tumor growth suppression. Although overproduced HO in cancerous tissues makes CDT a feasible and specific tumor therapeutic modality, the treatment outcomes of traditional chemodynamic agents still fall short of expectations. Reprogramming cellular metabolism is one of the hallmarks of tumors, which not only supports unrestricted proliferative demands in cancer cells, but also mediates the resistance of tumor cells against many antitumor modalities. Recent discoveries have revealed that various cellular metabolites including HO, iron, lactate, glutathione, and lipids have distinct effects on CDT efficiency. In this perspective, we intend to provide a comprehensive summary of how different endogenous molecules impact Fenton chemistry for a deep understanding of mechanisms underlying endogenous regulation-enhanced CDT. Moreover, we point out the current challenges and offer our outlook on the future research directions in this field. We anticipate that exploring CDT through manipulating metabolism will yield significant advancements in tumor treatment.
化学动力学疗法（CDT）是一种潜在的癌症治疗策略，它依靠芬顿化学反应将过氧化氢（H₂O₂）转化为具有高度细胞毒性的活性氧（ROS），以抑制肿瘤生长。尽管癌组织中过量产生的H₂O₂使CDT成为一种可行且特异的肿瘤治疗方式，但传统化学动力学试剂的治疗效果仍不尽人意。细胞代谢重编程是肿瘤的特征之一，它不仅支持癌细胞不受限制的增殖需求，还介导肿瘤细胞对多种抗肿瘤方式的抗性。最近的研究发现，包括H₂O₂、铁、乳酸、谷胱甘肽和脂质在内的各种细胞代谢物对CDT效率有不同影响。从这个角度出发，我们旨在全面总结不同内源性分子如何影响芬顿化学反应，以深入了解内源性调控增强型CDT的潜在机制。此外，我们指出了当前面临的挑战，并对该领域未来的研究方向提出展望。我们预计，通过调控代谢来探索CDT将在肿瘤治疗方面取得重大进展。
