生物相容性
卵巢癌
药物输送
化学
肿瘤微环境
癌细胞
化疗
三氧化二砷
癌症研究
背景(考古学)
药理学
癌症
细胞凋亡
医学
生物化学
生物
肿瘤细胞
内科学
古生物学
有机化学
作者
Mingzhu Ye,Roumei Ye,Yun Wang,Mengyu Guo,Minhui Zhu,Fengyue Yin,Y Wang,Xiaoqin Lai,Yu Wang,Zhongqun Qi,Jinling Wang,Dengyue Chen
标识
DOI:10.1016/j.ijpharm.2024.124426
摘要
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.
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