Copper-cysteamine nanoparticle-mediated microwave dynamic therapy improves cancer treatment with induction of ferroptosis

被引:46
作者
Zhou, Hui [1 ]
Liu, Zhongtao [1 ]
Zhang, Zijian [1 ]
Pandey, Nil Kanatha [2 ]
Amador, Eric [2 ]
Nguyen, William [2 ]
Chudal, Lalit [2 ]
Xiong, Li [1 ]
Chen, Wei [2 ]
Wen, Yu [1 ]
机构
[1] Cent South Univ, Xiangya Hosp 2, Dept Gen Surg, Changsha 410011, Peoples R China
[2] Univ Texas Arlington, Dept Phys, Arlington, TX 76019 USA
关键词
Cu-Cy; Microwave; PDT; Cell death; Colorectal cancer; Ferroptosis; PHOTODYNAMIC THERAPY; MECHANISMS;
D O I
10.1016/j.bioactmat.2022.12.023
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Photodynamic Therapy (PDT) holds a great promise for cancer patients, however, due to the hypoxic charac- teristics of most solid tumors and the limited penetration depth of light in tissues, the extensive clinical appli- cation of PDT is limited. Herein, we report microwave induced copper-cysteamine (Cu-Cy) nanoparticles-based PDT as a promising cancer treatment to overcome cancer resistance in combination with ferroptosis. The treatment efficiency of Cu-Cy-mediated microwave dynamic therapy (MWDT) tested on HCT15 colorectal cancer (CRC) cells via cell titer-blue cell viability assay and live/dead assay reveal that Cu-Cy upon MW irradiation can effectively destroy HCT15 CRC cells with average IC-50 values of 20 mu g/mL. The cytotoxicity of Cu-Cy to tumor cells after MW stimulation can be alleviated by ferroptosis inhibitor. Furthermore, Cu-Cy mediated MWDT could deplete glutathione peroxide 4 (GPX4) and enhance lipid peroxides (LPO) and malondialdehyde (MDA). Our findings demonstrate that MW-activated Cu-Cy killed CRC cells by inducing ferroptosis. The superior in vivo antitumor efficacy of the Cu-Cy was corroborated by a HCT15 tumor-bearing mice model. Immunohistochemical experiments showed that the GPX4 expression level in Cu-Cy + MW group was significantly lower than that in other groups. Overall, these findings demonstrate that Cu-Cy nanoparticles have a safe and promising clinical application prospect in MWDT for deep-seated tumors and effectively inhibit tumor cell proliferation by inducing ferroptosis, which provides a potential solution for cancer resistance.
引用
收藏
页码:322 / 330
页数:9
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