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.

Study of copper-cysteamine based X-ray induced photodynamic therapy and its effects on cancer cell proliferation and migration in a clinical mimic setting

Copper-cysteamine as a new generation of sensitizers can be activated by light,X-rays,microwaves,or ultrasound to produce reactive oxygen species.X-ray induced photodynamic therapy(X-PDT)has been studied extensively;however,most of the studies reported so far were conducted in the laboratory,which is not conducive to the clinical translation conditions.In this contribution,for the first time,we investigated the treatment efficiency of copper-cysteamine(Cu-Cy)based X-PDT by mimicking the clinical conditions with a clinical linear accelerator and building deep-seated tumor models to study not only the effectiveness but also its effects on the cell migration and proliferation in the level of the cell,tissue,and animal.The results showed that,without X-ray irradiation,Cu-Cy nanoparticles(NPs)had a low toxicity in HepG2,SK-HEP-1,Li-7,and 4T1 cells at a concentration below 100 mg/L.Interestingly,for the first time,it was observed that Cu-Cy mediated X-PDT can inhibit the proliferation and migration of these cell lines in a dose-dependent manner.Antigen markers of migration and cell proliferation,proliferating cell nuclear antigen(PCNA)and E-cadherin,from tumor tissue in the X-PDT group were remarkably different from that of the control group.Furthermore,the MRI assessment showed that the Cu-Cy based X-PDT inhibited the growth of deeply located tumors in mice and rabbits(p<0.05)without any obvious toxicities in vivo.Overall,these new findings demonstrate that Cu-Cy NPs have a safe and promising clinical application prospect in X-PDT to improve the efficiency of radiotherapy(RT)for deep-seated tumors and effectively inhibit tumor cell proliferation and migration.

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.

Aggregation-induced emission luminogens for highly effective microwave dynamic therapy

Aggregation-induced emission luminogens(AIEgens)exhibit efficient cytotoxic reactive oxygen species(ROS)generation capability and unique light-up features in the aggregated state,which have been well explored in image-guided photodynamic therapy(PDT).However,the limited penetration depth of light in tissue severely hinders AIEgens as a candidate for primary or adjunctive therapy for clinical applications.Coincidentally,microwaves(MWs)show a distinct advantage for deeper penetration depth in tissues than light.Herein,for the first time,we report AIEgen-mediated microwave dynamic therapy(MWDT)for cancer treatment.We found that two AIEgens(TPEPy-I and TPEPy-PF6)served as a new type of microwave(MW)sensitizers to produce ROS,including singlet oxygen(1O2),resulting in efficient destructions of cancer cells.The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and live/dead assays reveal that the two AIEgens when activated by MW irradiation can effectively kill cancer cells with average IC-50 values of 2.73 and 3.22μM,respectively.Overall,the ability of the two AIEgens to be activated by MW not only overcomes the limitations of conventional PDT,but also helps to improve existing MW ablation therapy by reducing the MW dose required to achieve the same therapeutic outcome,thus reducing the occurrence of side-effects of MW radiation.