Design Of Photothermal-Based Nanozymes And Application In Cancer Therapy

At present,radiotherapy and chemotherapy are the main means of clinical treatment of cancer,but there are problems such as large side effects and low cure rate.In recent years,some new treatment methods such as photothermal therapy,photodynamic therapy,and chemodynamic therapy have attracted much attention.Due to the inherent defects of the complex tumor microenvironment,it is difficult for a single treatment to completely inhibit tumor growth,and synergistic therapy can overcome the problem of poor efficacy of single therapy,thereby improving the efficacy of anti-tumor therapy.Nanozymes are widely used in biomedical fields due to their unique advantages such as controllable catalytic activity and good stability.Therefore,it is of great significance to design an efficient and multifunctional nanozyme to achieve the combination of multiple treatment methods.In this paper,three nanozymes based on photothermal function were designed and synthesized.The different enzyme activities,photothermal properties of materials and synergistic tumor treatment effects were studied.The research contents are summarized as follows:(1)The application of CuCoS nanozyme in photothermal therapy and chemodynamic therapy.Monodisperse CuCoS nanozyme was synthesized by hydrothermal method.The nanozyme is not only an excellent inorganic photothermal nanomaterial with good photothermal conversion performance,but also has peroxidase activity and glutathione oxidase activity.It can catalyze H2O2 in the tumor microenvironment to produce reactive oxygen species and scavenge reduced glutathione,thereby breaking the redox balance in tumor cells.Under near-infrared light 808 nm irradiation,the increase of temperature can increase the activity of the two enzymes and the enzyme reaction rate,thereby increasing the accumulation of reactive oxygen species and improving the anti-tumor effect.Therefore,CuCoS nanozymes can achieve a synergistic therapy of photothermal therapy and temperature-enhanced chemical kinetics,significantly inhibiting tumor proliferation.(2)Design of near-infrared controllable pyroptosis inducer and tumor immunotherapy.Uniform mesoporous Pt nanozymes were synthesized by solvothermal method,and glucose oxidase(GOx)was further loaded in the mesoporous channels.The outer layer of the material was further modified with thermosensitive material p(OEOMA-co-MEMA)(PCM)to obtain nanocomposite PCMPt/GOx.The material has the following advantages:(ⅰ)The thermosensitive material PCM can prevent the early leakage of GOx,reduce side effects,and improve the biocompatibility of the material.(ⅱ)Pt nanozymes not only have good photothermal properties,but also achieve precise and on-demand release of GOx controlled by near-infrared light.moreover,Pt nanozyme has catalase-like activity,which can consume H2O2 in the tumor microenvironment to produce O2 required for GOx catalytic reaction and improve hypoxia conditions.(ⅲ)The composite material can realize near-infrared light-controlled,heat-responsive pyroptosis and immune synergistic therapy.As an inducer of near-infrared controllable pyroptosis.PCMPt/GOx can activate the immune response in vivo.At the same time,mild photothermal can reverse the tumor immunosuppressive microenvironment and synergistically induce pyroptosis with immunotherapy,which has a good anti-tumor effect.(3)Application of ultra-small Pt nanozymes in tumor chemotherapy and photothermal therapy.The ultra-small Pt nanozyme with a particle size of less than 10 nm was successfully synthesized by hydrothermal method.It has good photothermal performance and catalase-like activity.It can react with H2O2 in the tumor microenvironment to produce O2 and improve hypoxic conditions.Subsequently,DSPE-PEG-NH2 was used to modify the surface of the material so that it could successfully load β-lapasone(β-LAP).After 808 nm laser irradiation,the increase of heat shock protein expression caused by photothermal and β-LAP can simultaneously activate quinone oxidoreductase l.The increase of enzyme activity consumes intracellular nicotinamide adenine dinucleotide phosphate and produces H2O2,causing oxidative damage.Pt@β-LAP nanoparticles can be combined with photothermal therapy and chemotherapy,which can be excreted through biological metabolism while significantly inhibiting tumor proliferation.