Study On The Application Of Gold-based Composite Nanomaterials In Photothermal-immunotherapy Of Tumors

The malignant tumor is harmful to human life and health.Traditional treatment,such as surgical resection,often can’t eliminate the tumor,there is a risk of recurrence and metastasis.With the development of medical treatment and science and technology,people have a deeper understanding of cancer cells,and a variety of new treatments such as targeted therapy,photothermal therapy,gene therapy,and immunotherapy are also available.Among them,photothermal therapy converts light energy into heat energy to kill cancer cells locally and induce tumor immunogenic cell death(ICD).However immune response elicited by ICD was insufficient to prevent relapse and metastasis because of the immunosuppressive tumor microenvironment(TME).Here,we use a T cell membrane to encapsulate near-infrared two(NIR-II)region photothermal materials to construct biomimetic T cell nanoparticles.Local hyperthermia produced by PTT induces ICD to recruit cytotoxic lymphocytes(CTL)to tumor sites for combined photothermal immunotherapy of tumors.Compared with T cells,biomimetic nanoparticles are smaller and easier to bind to tumor cell surface PDL1 through PD-1 on T cell membrane,which can effectively reduce tumor cells suppressing CTL immune activity through immune checkpoints,prevent CTL failure and enhance CTL immune response to tumor cells.In addition,similar to T cells,biomimetic nanoparticles target tumors through T cell membrane proteins,enhance tumor site accumulation and induce Fas L-dependent cancer cell apoptosis.The results show that the combined photothermal-immune therapy mediated by biomimetic nanoparticles can not only eliminate the primary tumor,but also increase the recruitment of tumor-infiltrating lymphocytes(TILs),produce memory T cells to inhibit distant untreated tumors,effectively prevent tumor recurrence,and provide the possibility for clinical effective treatment of cancer.Although PTT shows excellent anti-tumor properties,the high temperature produced by high-power laser burns the normal tissue near the tumor.To avoid this problem and achieve PTT at a lower temperature(less than 43 ℃),bovine serum albumin(BSA)was used as a template for biomineralization and loaded with capsaicin(Capsaicin).Finally,a gold nano-shell was formed on the surface of the nanoparticles,and a degradable near infrared zone two low-temperature photothermal induction immunotherapy nano-platform was constructed.The nano-platform can reduce the heat tolerance threshold of cancer cells through capsaicin,kill cancer cells and induce tumor ICD at low temperatures,and induce immune memory to prevent tumor recurrence.The activation of immune response mediated by photothermal therapy will have a farreaching impact on tumor immunotherapy strategies.At the same time,this method also provides a new idea for hypothermic photothermal therapy.