The fluorescence quenching spectra of the holo-Cu A and apo-Cu A domain of cytochrome c oxidase from Para coccus versutus by KI were investigated.The results indicated that in solution part of the fluorophore tryptoph...The fluorescence quenching spectra of the holo-Cu A and apo-Cu A domain of cytochrome c oxidase from Para coccus versutus by KI were investigated.The results indicated that in solution part of the fluorophore tryptophanes of the Cu A domain are exposed to the surface of the protein,and others buried inside o f the hydrophobic core.The fluorescence quenching constants of holo-Cu A and apo-Cu A domain protein by KI are1.39and2.24,respectively,which suggested t hat the bi-nuclear copper center[Cu A+1.5 -Cu A+1.5 ]also plays a role on the structural stability of the protein.展开更多
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 applicati...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.展开更多
文摘The fluorescence quenching spectra of the holo-Cu A and apo-Cu A domain of cytochrome c oxidase from Para coccus versutus by KI were investigated.The results indicated that in solution part of the fluorophore tryptophanes of the Cu A domain are exposed to the surface of the protein,and others buried inside o f the hydrophobic core.The fluorescence quenching constants of holo-Cu A and apo-Cu A domain protein by KI are1.39and2.24,respectively,which suggested t hat the bi-nuclear copper center[Cu A+1.5 -Cu A+1.5 ]also plays a role on the structural stability of the protein.
基金the support by the Natural Science Foundation of China(81773293,81873640,81970569,82000756)Natural Science Foundation of Hunan Province,No.2022JJ40700+2 种基金the Key Project of Science and Technology Program of Hunan Provincial Science and Technology Department(2015GK3117,2017WK2063)the supports from Guangxi Jialouyuan Medical Inc.,Solgrothe distinguished award from UT Arlington as well as ROSFORCURE Inc.
文摘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.
