Study On The Construction Of Heat Shock Protein-inhibited Photothermal Platform Based On Two-dimensional Ti₃C₂（MXene） And Its Photothermal Effect

Since the 21st century,cancer has become one of the most important causes of human death,and tens of millions of people are diagnosed with cancer every year,posing a serious threat to people’s life and health.Nowadays,the main clinical treatments for cancer are surgery,radiotherapy and chemotherapy,but these methods are risky,have obvious side effects and can destroy the immune system,and have a high possibility of recurrence.Photothermal therapy,as a new cancer treatment method,has attracted interest in cancer treatment due to its non-invasive and non-contact nature,and the rapid development of nanomaterials technology is laying a solid foundation for photothermal therapy to become an alternative cancer treatment method.Photothermal therapy is a treatment that converts light energy into heat energy by irradiating the tumor site enriched with nano-photothermics using near-infrared light,thus generating high temperature to thermally ablate tumor cells.However,in order to attenuate the damage caused by high temperature,tumor cells will activate their self-protection mechanism and activate the anti-apoptotic program of cancer cells in a hot environment.Therefore,in order to enhance the heat sensitivity of cancer cells,the concentration of photothermal converters can be changed,the excitation light power density can be increased or repeated light exposure can be performed,but these methods can cause irreversible damage such as dose-dependent toxicity and inflammation,which can harm the nearby normal cells and healthy tissues.Therefore,how to reduce the heat resistance of cells is still an urgent problem to be solved.MXene,as a novel two-dimensional nanomaterial,has become a hot research topic due to its excellent physicochemical properties,large surface area,and its diverse functional groups on the surface.Moreover,compared with other two-dimensional materials,MXene has excellent hydrophilicity and easy surface modification,which makes it easier to be applied in biomedical fields.In this work,we developed a novel Ti₃C₂@Qu nanocomposite,which can be applied to heat shock protein-inhibited photothermal therapy and effectively improve the therapeutic effect of photothermal therapy.The details of the study are as follows:1.First,we obtained small-sized thin nanosheets with sizes around 200-300 nm and thicknesses around 2.5 nm,which can be applied in biomedicine,by two-step etching method of MAX phase.Then surface modification of the nanosheets by electrostatic adsorption with quercetin modified by polyvinylpyrrolidone to obtain the desired material,Ti₃C₂@Qu.The morphology as well as physicochemical properties of the composites were investigated using SEM,TEM,XRD and other characterization methods.Then,the visible-near-infrared absorption spectra were tested to calculate the extinction coefficients,and the photothermal conversion ability and photothermal stability of the composites were investigated in vitro by varying the solution concentration and excitation optical power density,and the release behavior of quercetin was studied by simulating the acidic microenvironment of the tumor.The results showed that the composite had excellent extinction coefficient[21.75 L/（g·cm）]and photothermal conversion efficiency（31.34%）,and could release quercetin in large amounts in the acidic environment,which achieved our expected results and could be applied in subsequent experiments.2.Subsequently,we explored the biosafety and photothermal therapeutic effects of the material at the cellular level.The cytotoxicity of the material was evaluated using melanoma cells B16 as a cellular model,and the results of MTT experiments showed that the composite material was biosafe under normal environmental culture,with a cell survival rate of 87.31%even at a material concentration of 100μg/m L,and a cell survival rate of 17.68%under 808 nm near-infrared light excitation,which is a significant improvement compared to nanosheets alone.After observing the mitochondrial and nuclear staining of cells in different groups,it was clearly observed that the composite Ti₃C₂@Qu accelerated the process of apoptosis by inhibiting the overexpression of heat shock proteins and sensitized the photothermal treatment.Finally,a tumor-bearing mouse model was established to investigate the anti-tumor effect of the composite material at the biological level.Through the treatment and observation process,it can be found that the material effectively inhibits the tumor in mice and has more excellent biocompatibility,which lays a good foundation for other subsequent in vivo experiments.