Department of Urology, Kidney and Urology Center, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China; Scientific Research Center, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
Department of Urology, Kidney and Urology Center, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
J Colloid Interface Sci. 2022 Dec 15;628(Pt B):864-876. doi: 10.1016/j.jcis.2022.08.110. Epub 2022 Aug 19.
Drug delivery based on abnormal features of the tumor microenvironment (TME) has attracted considerable interest worldwide. In this study, we proposed an applicable strategy to increase the reactive oxygen species (ROS) and inhibit glutathione (GSH), in an effort to amplify oxidative damage in prostate cancer cells. Specifically, we developed dual-responsive supramolecular self-assembled nanoparticles (NPs) based on polymerized methacrylic acid (MA) and polymerized poly(ethylene glycol) dimethyl acrylate-modified β-cyclodextrin (CD) with ferrocene (Fc)-connected (S) (+)-camptothecin (CPT) (designated as MA-CD/Fc-CPT NPs). The as-prepared negatively charged supramolecular NPs can be taken up by tumor cells successfully owing to their reversible negative-to-positive charge transition capacity at acidic pH. The supramolecular NPs increased ROS generation and decreased GSH to amplify oxidative stress and improve the therapeutic effect of chemotherapy. As expected, MA-CD/Fc-CPT NPs displayed good drug delivery capabilities to tumor cells or tissues. MA-CD/Fc-CPT NPs also inhibited cancer cell proliferation in both the cells and tissues. This result was partially due to increased ROS generation and decreased GSH, which contributed to more pronounced oxidative stress. The as-prepared supramolecular NPs displayed great biosafety to normal tissues. According to our results, negatively charged supramolecular MA-CD/Fc-CPT NPs are well-suited for drug delivery and improved cancer treatment in TMEs.
基于肿瘤微环境（TME）异常特征的药物输送在全球范围内引起了相当大的兴趣。在这项研究中，我们提出了一种可行的策略，以增加活性氧（ROS）并抑制谷胱甘肽（GSH），努力放大前列腺癌细胞中的氧化损伤。具体而言，我们开发了基于聚合甲基丙烯酸（MA）和聚合聚乙二醇二甲基丙烯酸酯修饰的β-环糊精（CD）与二茂铁（Fc）连接的（S）（+）-喜树碱（CPT）（命名为 MA-CD/Fc-CPT NPs）的双响应超分子自组装纳米颗粒（NPs）。由于其在酸性 pH 值下可逆的负到正电荷转换能力，制备的带负电荷的超分子 NPs 可以被肿瘤细胞成功摄取。超分子 NPs 通过增加 ROS 的产生和降低 GSH 来放大氧化应激并提高化疗的治疗效果。不出所料，MA-CD/Fc-CPT NPs 对肿瘤细胞或组织表现出良好的药物递送能力。MA-CD/Fc-CPT NPs 还抑制了细胞和组织中的癌细胞增殖。这一结果部分归因于 ROS 的产生增加和 GSH 的减少，这导致了更明显的氧化应激。所制备的超分子 NPs 对正常组织具有良好的生物安全性。根据我们的结果，带负电荷的超分子 MA-CD/Fc-CPT NPs 非常适合在 TME 中进行药物输送和改善癌症治疗。
