State Key Laboratory of Metastable Materials Science and Technology, Nano-biotechnology Key Lab of Hebei Province, Applying Chemistry Key Lab of Hebei Province, Yanshan University, Qinhuangdao 066004, PR China.
School of Sciences, Hebei University of Science and Technology, Shijiazhuang 050018, PR China.
J Colloid Interface Sci. 2024 Jun;663:1064-1073. doi: 10.1016/j.jcis.2024.03.013. Epub 2024 Mar 4.
Doxorubicin (DOX) is widely used in clinic as a broad-spectrum chemotherapy drug, which can enhance the efficacy of chemodynamic therapy (CDT) by interfering tumor-related metabolize to increase HO content. However, DOX can induce serious cardiomyopathy (DIC) due to its oxidative stress in cardiomyocytes. Eliminating oxidative stress would create a significant opportunity for the clinical application of DOX combined with CDT. To address this issue, we introduced sodium ascorbate (AscNa), the main reason is that AscNa can be catalyzed to produce HO by the abundant Fe in the tumor site, thereby enhancing CDT. While the content of Fe in heart tissue is relatively low, so the oxidation of AscNa had tumor specificity. Meanwhile, due to its inherent reducing properties, AscNa could also eliminate the oxidative stress generated by DOX, preventing cardiotoxicity. Due to the differences between myocardial tissue and tumor microenvironment, a novel nanomedicine was designed. MoS was employed as a carrier and CDT catalyst, loaded with DOX and AscNa, coating with homologous tumor cell membrane to construct an acid-responsive nanomedicine MoS-DOX/AscNa@M (MDA@M). In tumor cells, AscNa enhances the synergistic therapy of DOX and MoS. In cardiomyocytes, AscNa could effectively reduce the cardiomyopathy induced by DOX. Overall, this study enhanced the clinical potential of chemotherapy synergistic CDT.
阿霉素（DOX）作为一种广谱化疗药物，在临床上被广泛应用，它可以通过干扰肿瘤相关代谢来增加 HO 含量，增强化学动力学治疗（CDT）的疗效。然而，由于 DOX 在心肌细胞中产生氧化应激，会导致严重的心肌病（DIC）。消除氧化应激为 DOX 联合 CDT 的临床应用创造了重要机会。为了解决这个问题，我们引入了抗坏血酸钠（AscNa），主要原因是 AscNa 可以在肿瘤部位丰富的 Fe 催化下产生 HO，从而增强 CDT。而心肌组织中 Fe 的含量相对较低，因此 AscNa 的氧化具有肿瘤特异性。同时，由于其固有还原性质，AscNa 还可以消除 DOX 产生的氧化应激，防止心脏毒性。由于心肌组织和肿瘤微环境的差异，设计了一种新型纳米药物。MoS 被用作载体和 CDT 催化剂，负载 DOX 和 AscNa，用同源肿瘤细胞膜包裹，构建了一种酸响应纳米药物 MoS-DOX/AscNa@M（MDA@M）。在肿瘤细胞中，AscNa 增强了 DOX 和 MoS 的协同治疗作用。在心肌细胞中，AscNa 可以有效减轻 DOX 引起的心肌病。总的来说，这项研究增强了化疗协同 CDT 的临床潜力。
