近年来，三氧化二砷（ATO）在卵巢癌化疗中的使用引起了广泛关注。然而，ATO的生物相容性有限以及严重的毒副作用的发生阻碍了其临床应用。本研究报道了一种使用 ATO 作为治疗剂的纳米颗粒 (NP) 药物递送系统。通过联合饥饿疗法、化学动力学疗法和化疗来达到协同作用来治疗卵巢癌是该系统的最终目标。这种基于纳米技术的药物输送系统 (NDDS) 将砷锰复合物引入癌细胞，导致随后释放致命的砷离子 (As3) 和锰离子 (Mn2)。肿瘤的酸性微环境促进了这一过程，MR 成像可以实时监测 ATO 剂量分布。同时，为了产生活性氧，通过类芬顿反应诱导细胞死亡，Mn2 利用了肿瘤细胞内过剩的过氧化氢 (H2O2)。基于葡萄糖氧化酶的饥饿疗法进一步支持了这一机制，恢复了 H2O2 并降低了细胞酸度。因此，这种方法实现了自我增强的化学动力学治疗。通过使用封装 NP 的 SKOV3 细胞膜，促进了 NP 的同源靶向。因此，与 ATO 的非特异性给药相比，使用整合了 ATO 递送、治疗和监测的多模式 NDDS 表现出优越的功效和生物相容性。这种方法为卵巢癌的诊断和治疗提出了一个新概念。版权所有 © 2024。由 Elsevier B.V. 出版。

In recent years, the use of arsenic trioxide (ATO) in the context of ovarian cancer chemotherapy has attracted significant attention. However, ATO's limited biocompatibility and the occurrence of severe toxic side effects hinder its clinical application. A nanoparticle (NP) drug delivery system using ATO as a therapeutic agent is reported in this study. Achieving a synergistic effect by combining starvation therapy, chemodynamic therapy, and chemotherapy for the treatment of ovarian cancer was the ultimate goal of this system. This nanotechnology-based drug delivery system (NDDS) introduced arsenic-manganese complexes into cancer cells, leading to the subsequent release of lethal arsenic ions (As3+) and manganese ions (Mn2+). The acidic microenvironment of the tumor facilitated this process, and MR imaging offered real-time monitoring of the ATO dose distribution. Simultaneously, to produce reactive oxygen species that induced cell death through a Fenton-like reaction, Mn2+ exploited the surplus of hydrogen peroxide (H2O2) within tumor cells. Glucose oxidase-based starvation therapy further supported this mechanism, which restored H2O2 and lowered the cellular acidity. Consequently, this approach achieved self-enhanced chemodynamic therapy. Homologous targeting of the NPs was facilitated through the use of SKOV3 cell membranes that encapsulated the NPs. Hence, the use of a multimodal NDDS that integrated ATO delivery, therapy, and monitoring exhibited superior efficacy and biocompatibility compared with the nonspecific administration of ATO. This approach presents a novel concept for the diagnosis and treatment of ovarian cancer.Copyright © 2024. Published by Elsevier B.V.