The Application Of Pt(Ⅳ)-Loaded Hollow Copper Sulfide Nanocubes In The Treatment Of Colorectal Cancer

Colorectal cancer（CRC）is the second leading cause of cancer death and the third leading cause of cancer death worldwide.At present,the main treatment of CRC is surgery and chemotherapy（CT）.However,non-specific distribution,multidrug resistance and other shortcomings limit the application of chemotherapy drugs.Fortunately,the emergence of nanomaterials has brought great development to biomedical fields such as drug delivery and disease diagnosis.Copper sulfide（Cu S）nanoparticles are an inorganic semiconductor material with near-infrared response.They have simple preparation,high stability,low raw material cost,good biocompatibility and excellent optical properties.Therefore,Cu S nanoparticles have been widely used in photodynamic therapy（PDT）and photothermal therapy（PTT）.In addition,as a chemotherapeutic drug,ethylenediamine platinum chloride（II）can bind to cancer cell DNA and cause damage to tumor cells.In this study,we prepared a hollow cubic Cu S nanoparticles loaded with Pt（IV）（oxidized cis-ethylenediamine platinum chloride（II））drug.Pt（IV）drug was successfully loaded on Cu S nanoparticles through physical adsorption and electrostatic interaction to obtain Pt（IV）-Cu S nanoparticles.In order to improve the stability of nanoparticles in vivo circulation,m PEG₂₀₀₀-NH₂ was modified on the surface of Pt（IV）-Cu S by Cu-N coordination to obtain Pt（IV）-Cu S@PEG nanoparticles.Under near-infrared laser（NIR）irradiation,Cu S produced excellent PTT and PDT effects.However,the high concentration of glutathione（GSH）in cancer cells consumes reactive oxygen species（ROS）produced by Cu S and reduces the PDT effect.Therefore,we introduced Pt（IV）drug,and Pt（IV）was successfully taken up by cancer cells under the loading of Cu S.Pt（IV）is reduced to more toxic Pt（II）under the action of intracellular GSH,which not only has CT effect,but also promotes PDT of Cu S,and has a combined therapeutic effect.Transmission electron microscopy,hydrated particle size,potential and other characterization results proved that Pt（IV）-Cu S@PEG nanoparticles were successfully prepared.The in vitro photothermal properties and ROS generation ability of Pt（IV）-Cu S@PEG nanoparticles were evaluated,indicating that they have excellent PTT and PDT effects.The results of cell experiments showed that Pt（IV）-Cu S@PEG nanoparticles had good biocompatibility.Under NIR irradiation,it showed excellent CT/PTT/PDT combined therapeutic effect and successfully induced apoptosis of HTC-116 cells.All experimental results show that we have successfully synthesized a highly biocompatible Pt（IV）-Cu S@PEG nanoparticle,which is expected to be used for CT/PTT/PDT combined treatment of colon cancer.