阿霉素
光热治疗
化疗
癌症研究
缺氧(环境)
细胞凋亡
化学
程序性细胞死亡
联合疗法
肿瘤缺氧
肿瘤微环境
药理学
放射治疗
医学
材料科学
生物化学
肿瘤细胞
纳米技术
外科
氧气
有机化学
作者
Wei-Nan Zhao,Jianghao Xing,Min Wang,Hongjuan Li,Shi‐Gang Sun,Xianwen Wang,Yongqian Xu
标识
DOI:10.1016/j.ijbiomac.2024.130785
摘要
Chemotherapy remains one of the most widely used cancer treatment modalities in clinical practice. However, the characteristic microenvironment of solid tumors severely limits the anticancer efficacy of chemotherapy. In addition, a single treatment modality or one death pathway reduces the antitumor outcome. Herein, tumor-targeting O2 self-supplied nanomodules (CuS@DOX/CaO2-HA) are proposed that not only alleviate tumor microenvironmental hypoxia to promote the accumulation of chemotherapeutic drugs in tumors but also exert photothermal effects to boost drug release, penetration and combination therapy. CuS@DOX/CaO2-HA consists of copper sulfide (CuS)-loaded calcium peroxide (CaO2) and doxorubicin (DOX), and its surface is further modified with HA. CuS@DOX/CaO2-HA underwent photothermal treatment to release DOX and CaO2. Hyperthermia accelerates drug penetration to enhance chemotherapeutic efficacy. The exposed CaO2 reacts with water to produce Ca2+, H2O2 and O2, which sensitizes cells to chemotherapy through mitochondrial damage caused by calcium overload and a reduction in drug efflux via the alleviation of hypoxia. Moreover, under near infrared (NIR) irradiation, CuS@DOX/CaO2-HA initiates a pyroptosis-like cell death process in addition to apoptosis. In vivo, CuS@DOX/CaO2-HA demonstrated high-performance antitumor effects. This study provides a new strategy for synergistic enhancement of chemotherapy in hypoxic tumor therapy via combination therapy and multiple death pathways.
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