活性氧是肿瘤化学动力学治疗具有突出效果的关键，但是肿瘤组织缺氧和高浓度谷胱甘肽的微环境阻碍了活性氧的产生。
近日，湖北大学张成教授和杨勇教授等人在Science China Materials发表研究论文，构建了透明质酸修饰和过氧单硫酸盐负载的中空二氧化锰纳米颗粒（HA@HMn/PMS）。该体系不仅可以实现肿瘤微环境响应性药物释放，而且还可作为活性氧供体来增强肿瘤化学动力学疗效。
本文要点
1) HA@HMn/PMS在肿瘤部位富集后，消耗局部谷胱甘肽并将二氧化锰还原为二价锰离子，然后通过类芬顿反应和催化过氧单硫酸盐分别生成·OH和·SO4−自由基.2) ·SO4−是一种罕见的自由基，具有优异的氧化能力和非氧依赖特性，它的产生和作用打破了传统活性氧的局限性，并且可以对肿瘤细胞造成严重的损伤。3) 在异植瘤小鼠模型中，研究表明HA@HMn/PMS能够显著抑制小鼠肿瘤生长。本研究通过结合谷胱甘肽的消耗和多种自由基在肿瘤治疗中的协同作用，激发了化学动力学治疗在多功能纳米系统应用方向的潜力。
Figure 1. Preparation and in vivo anti-tumor therapy of HA@HMn/PMS. (a) Schematic diagram of the preparation process of HA@HMn/PMS. (b) Schematic illustration of the antitumor therapy mediated by HA@HMn/PMS.Figure 2. Characterization of the prepared materials. (a) SEM images of SiO2, MnO2@SiO2, HMn, and HA@HMn/PMS. (b) TEM image of HMn. (c) TEM image of HA@HMn/PMS. (d) Zeta potential of the prepared nanoparticles. (e) Hydrodynamic size of the prepared nanoparticles. (f) XPS spectra of Mn 2p in HMn nanoparticles. (g) N2 absorption-desorption isotherm of HMn. (h) FTIR spectra of HMn, HA@HMn, and HA@HMn/PMS. (i) GSH degradation rate in HA@HMn/PMS mixture detected by DTNB. (j) Time-dependent degradation rate of GSH. (k) Hemolysis test of HA@HMn/PMS with different concentrations. (l) The UV-vis absorption spectra of MB after different treatments. (m) The UV-vis absorption spectra of MB at different concentrations of HA@HMn/PMS.![]()
Figure 3. Cytotoxicity test in vitro. (a) Cell viability of CT26 cells treated with HA@HMn and HA@HMn/PMS. (b) Cell viability of 293T and CT26 cells after incubation with different concentrations of HA@HMn/PMS. (c) Cell viability of CT26 cells after incubation with HA@HMn/PMS for different time. (d) Live and dead double-staining images of CT26 cells after different treatments. (e) Flow cytometry analysis for evaluating the apoptosis of Annexin V-FITC/PI-stained CT26 cells after different treatments.Figure 4. In vivo biosafety evaluation. (a) Blood routine assay, (b) liver function-related enzyme concentration and (c) kidney function-related substrate concentration at various time points after intravenous injection of HA@HMn/PMS. (d) H&E staining of the major organs (heart, liver, spleen, lung, and kidney) in each group after different treatments.Dejie Ge, Debao Ren, Yamin Duan, Xuan Luo, Shuailin He, Wenjun Qin, Fei Wang, Wen Yin, Lixin Ma, Yong Yang, Cheng Zhang. Hollow MnO2-based multifunctional nanoplatform for enhanced tumor chemodynamic therapy. Sci. China Mater. (2024).https://doi.org/10.1007/s40843-024-3177-5
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