School of Materials and Chemistry, University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai 200093, China.
Molecules. 2023 Jun 1;28(11):4498. doi: 10.3390/molecules28114498.
The specificity of the tumor microenvironment (TME) severely limits the effectiveness of tumor treatment. In this study, we prepared a composite nanoparticle of manganese dioxide and selenite by a one-step redox method, and their stability under physiological conditions was improved with a bovine serum protein modification to obtain MnO/Se-BSA nanoparticles (SMB NPs). In the SMB NPs, manganese dioxide and selenite endowed the SMB NPs with acid-responsive and catalytic, and antioxidant properties, respectively. The weak acid response, catalytic activity, and antioxidant properties of composite nanoparticles were verified experimentally. Moreover, in an in vitro hemolysis assay, different concentrations of nanoparticles were incubated with mouse erythrocytes, and the hemolysis ratio was less than 5%. In the cell safety assay, the cell survival ratio was as high as 95.97% after the co-culture with L929 cells at different concentrations for 24 h. In addition, the good biosafety of composite nanoparticles was verified at the animal level. Thus, this study helps to design high-performance and comprehensive therapeutic reagents that are responsive to the hypoxia, weak acidity, hydrogen peroxide overexpression nature of TME and overcome the limitations of TME.
肿瘤微环境（TME）的特异性严重限制了肿瘤治疗的效果。在本研究中，我们通过一步氧化还原法制备了二氧化锰和亚硒酸盐的复合纳米粒子，并通过牛血清蛋白修饰提高了其在生理条件下的稳定性，得到了 MnO/Se-BSA 纳米粒子（SMB NPs）。在 SMB NPs 中，二氧化锰和亚硒酸盐分别赋予 SMB NPs 酸响应和催化以及抗氧化特性。实验验证了复合纳米粒子的弱酸响应、催化活性和抗氧化性能。此外，在体外溶血试验中，不同浓度的纳米粒子与小鼠红细胞孵育，溶血率小于 5%。在细胞安全性试验中，不同浓度共培养 24 h 后，L929 细胞的细胞存活率高达 95.97%。此外，在动物水平上验证了复合纳米粒子的良好生物安全性。因此，这项研究有助于设计对 TME 的缺氧、弱酸性、过氧化氢过表达性质具有响应性的高性能、综合治疗试剂，克服 TME 的局限性。
