Hao Ji-Na, Ge Kaiming, Chen Guoli, Dai Bin, Li Yongsheng
Lab of Low Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontier Science Center of the Materials Biology and Dynamic Chemistry, Shanghai Engineering Research Center of Hierarchical Nanomaterials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
School of Chemistry and Chemical Engineering, Pharmacy School, State Key Laboratory Incubation Base for Green Processing of Chemical Engineering, Shihezi University, Shihezi 832003, China.
Chem Soc Rev. 2023 Nov 13;52(22):7707-7736. doi: 10.1039/d3cs00356f.
Chemodynamic therapy (CDT) is a newly developed cancer-therapeutic modality that kills cancer cells by the highly toxic hydroxyl radical (˙OH) generated from the triggered Fenton/Fenton-like reactions in an acidic and HO-overproduced tumor microenvironment (TME). By taking the advantage of the TME-activated catalytic reaction, CDT enables a highly specific and minimally-invasive cancer treatment without external energy input, whose efficiency mainly depends on the reactant concentrations of both the catalytic ions and HO, and the reaction conditions (including pH, temperature, and amount of glutathione). Unfortunately, it suffers from unsatisfactory therapy efficiency for clinical application because of the limited activators (, mild acid pH and insufficient HO content) and overexpressed reducing substance in TME. Currently, various synergistic strategies have been elaborately developed to increase the CDT efficiency by regulating the TME, enhancing the catalytic efficiency of catalysts, or combining with other therapeutic modalities. To realize these strategies, the construction of diverse nanocarriers to deliver Fenton catalysts and cooperatively therapeutic agents to tumors is the key prerequisite, which is now being studied but has not been thoroughly summarized. In particular, nanocarriers that can not only serve as carriers but are also active themselves for therapy are recently attracting increasing attention because of their less risk of toxicity and metabolic burden compared to nanocarriers without therapeutic capabilities. These therapy-active nanocarriers well meet the requirements of an ideal therapy system with maximum multifunctionality but minimal components. From this new perspective, in this review, we comprehensively summarize the very recent research progress on nanocarrier-based systems for enhanced CDT and the strategies of how to integrate various Fenton agents into the nanocarriers, with particular focus on the studies of therapy-active nanocarriers for the construction of CDT catalysts, aiming to guide the design of nanosystems with less components and more functionalities for enhanced CDT. Finally, the challenges and prospects of such a burgeoning cancer-theranostic modality are outlooked to provide inspirations for the further development and clinical translation of CDT.
化学动力疗法(CDT)是一种新开发的癌症治疗方式,它通过在酸性和过氧化氢过量产生的肿瘤微环境(TME)中触发的芬顿/类芬顿反应产生的高毒性羟基自由基(˙OH)来杀死癌细胞。通过利用TME激活的催化反应,CDT无需外部能量输入即可实现高度特异性和微创性的癌症治疗,其效率主要取决于催化离子和过氧化氢的反应物浓度以及反应条件(包括pH值、温度和谷胱甘肽含量)。不幸的是,由于激活剂有限(温和的酸性pH值和过氧化氢含量不足)以及TME中还原物质的过度表达,其临床应用的治疗效率并不理想。目前,已经精心开发了各种协同策略,通过调节TME、提高催化剂的催化效率或与其他治疗方式相结合来提高CDT效率。为了实现这些策略,构建多种纳米载体以将芬顿催化剂和协同治疗剂递送至肿瘤是关键前提,目前这方面正在研究中,但尚未得到全面总结。特别是,那些不仅可以作为载体而且自身具有治疗活性的纳米载体,由于与不具有治疗能力的纳米载体相比,其毒性和代谢负担风险较小,最近受到越来越多的关注。这些具有治疗活性的纳米载体很好地满足了理想治疗系统的要求,即具有最大的多功能性但组件最少。从这个新的角度出发,在本综述中,我们全面总结了基于纳米载体的增强型CDT系统的最新研究进展以及将各种芬顿试剂整合到纳米载体中的策略,特别关注用于构建CDT催化剂的具有治疗活性的纳米载体的研究,旨在指导设计具有更少组件和更多功能的纳米系统以增强CDT。最后,展望了这种新兴的癌症诊疗方式所面临的挑战和前景,以为CDT的进一步发展和临床转化提供启示。
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