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

Photodynamic Therapy(PDT)holds a great promise for cancer patients,however,due to the hypoxic characteristics of most solid tumors and the limited penetration depth of light in tissues,the extensive clinical application 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 20μg/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.

Use of copper-cysteamine nanoparticles to simultaneously enable radiotherapy,oxidative therapy and immunotherapy for melanoma treatment

Dear Editor,Melanoma,squamous cell carcinoma(SCC),and basal cell carcinoma(BCC)are three major types of skin cancer.Among them,melanoma is the most severe form and accounts for~4%of all newly diagnosed cancers annually in the United States.It is estimated that approximately 9500 people are diagnosed with skin cancer every day,and more than 1 million Americans are living with melanoma.Melanoma treatment is still a major challenge in the clinic.Photodynamic therapy(PDT)is composed of targeted ablation and immune activation,is less invasive than other therapies and has been widely used in the treatment of various cancers.