66571Tianjin First Central Hospital, Tianjin, China.
Renji Hospital South Campus, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Technol Cancer Res Treat. 2022 Jan-Dec;21:15330338221095670. doi: 10.1177/15330338221095670.
The tumor microenvironment is complex and changeable, so the design of a nano-delivery system for the tumor microenvironment has attracted wide attention. Based on this, we designed an intelligent nano-reactor for the characteristics of acidic pH and hypoxia in the tumor microenvironment. Firstly, the silver nano-balls were synthesized by the biological template method, which exhibited a good photothermal conversion efficiency and can realize the photothermal treatment of tumor sites. Subsequently, the hypoxic prodrug tirapazamine (TPZ) and polydopamine (PDA) for chemotherapy were self-assembled. After PDA arrived at the tumor site (pH 5.5) from the normal physiological environment (pH 7.4), the hypoxic prodrug TPZ was released in pH response by PDA. Subsequently, TPZ selectively induced obvious cell damage under tumor hypoxia stimulation but had no toxic effect on normal cells under normal oxygen. In addition, the nano-converter was loaded with iRGD on the surface, which enhanced the targeted delivery of the nano-reactor to achieve a highly effective antitumor effect. The nano-reactor was capable of combining photothermal/chemotherapy therapy. Importantly, it can selectively kill tumor cells without damaging normal cells based on the characteristics of the tumor microenvironment, with high bio-safety and clinical transformation potential.
肿瘤微环境复杂多变，因此针对肿瘤微环境的纳米递药系统设计受到了广泛关注。基于此，我们针对肿瘤微环境酸性 pH 值和缺氧的特点设计了一种智能纳米反应器。首先，通过生物模板法合成了银纳米球，其表现出良好的光热转换效率，能够实现肿瘤部位的光热治疗。随后，将缺氧前药替拉扎明（TPZ）和用于化疗的聚多巴胺（PDA）自组装。当 PDA 从正常生理环境（pH7.4）到达肿瘤部位（pH5.5）时，PDA 通过 pH 响应释放缺氧前药 TPZ。随后，TPZ 在肿瘤缺氧刺激下选择性地诱导明显的细胞损伤，但在正常氧下对正常细胞没有毒性作用。此外，纳米转化器表面负载 iRGD，增强了纳米反应器的靶向递送，实现了高效的抗肿瘤效果。该纳米反应器能够结合光热/化疗治疗。重要的是，它可以根据肿瘤微环境的特点选择性地杀死肿瘤细胞而不损伤正常细胞，具有较高的生物安全性和临床转化潜力。
