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.

Colorectal liver metastasis:molecular mechanism and interventional therapy

Colorectal cancer(CRC)is one of the most frequently occurring malignancy tumors with a high morbidity additionally,CRC patients may develop liver metastasis,which is the major cause of death.Despite significant advances in diagnostic and therapeutic techniques,the survival rate of colorectal liver metastasis(CRLM)patients remains very low.CRLM,as a complex cascade reaction process involving multiple factors and procedures,has complex and diverse molecular mechanisms.In this review,we summarize the mechanisms/pathophysiology,diagnosis,treatment of CRLM.We also focus on an overview of the recent advances in understanding the molecular basis of CRLM with a special emphasis on tumor microenvironment and promise of newer targeted therapies for CRLM,further improving the prognosis of CRLM patients.