Zhu Fukai, Huang Cailin, Lin YanLing, Li Yang, Tu Ruiqin, Lu Weihong
Department of Gynecology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, 361015, China.
Engineering Technological Center of Mushroom Industry, Minnan Normal University, Zhangzhou, Fujian 363000, China.
Biomater Sci. 2023 Oct 24;11(21):7132-7145. doi: 10.1039/d3bm00994g.
Synergistic chemo-phototherapy has offered tremendous potential in cancer treatment. Nevertheless, nanosystems usually suffer from the complexity of multicomponents (polymeric or inorganic materials), which results in carrier-related toxicity issues. Moreover, the GSH over-expression of tumor cells seriously compromises ROS therapeutic efficiency. Herein, we designed a self-delivered nanodrug Cu(II) coordination-driven co-self-assembly of celastrol (CST, a chemo-drug with anti-angiogenesis activity) and indocyanine green (ICG, a photosensitizer) for synergistic chemo-phototherapy with GSH depletion. The nanodrug was further cloaked by an erythrocyte membrane (RBC) to prolong the circulation time. Within the tumor microenvironment, the nanodrug would be disassembled upon intracellular GSH triggering. Moreover, the released Cu(II) could efficiently deplete the GSH, thus damaging the ROS-scavenging system and amplifying the phototherapeutic efficiency upon laser irradiation. The experiments validated the highly effective accumulation at tumor sites, potent tumor growth inhibition, and inappreciable systemic toxicity. The tumor microenvironment-responsive coordination-driven self-assembled biomimetic nanodrug may hold potential applications in tumor theranostics.
协同化学光热疗法在癌症治疗中展现出了巨大潜力。然而，纳米系统通常存在多组分（聚合物或无机材料）的复杂性问题，这导致了与载体相关的毒性问题。此外，肿瘤细胞中谷胱甘肽（GSH）的过度表达严重影响了活性氧（ROS）的治疗效率。在此，我们设计了一种自递送纳米药物，通过铜（II）配位驱动，使具有抗血管生成活性的化学药物雷公藤红素（CST）与吲哚菁绿（ICG，一种光敏剂）共同自组装，用于协同化学光热疗法并消耗GSH。该纳米药物进一步用红细胞膜（RBC）包裹以延长循环时间。在肿瘤微环境中，纳米药物会在细胞内GSH触发下分解。此外，释放出的铜（II）能够有效消耗GSH，从而破坏ROS清除系统，并在激光照射下增强光热治疗效率。实验验证了该纳米药物在肿瘤部位的高效积累、强大的肿瘤生长抑制能力以及微不足道的全身毒性。这种肿瘤微环境响应性配位驱动自组装的仿生纳米药物可能在肿瘤诊疗中具有潜在应用。
