Antigen-Capturing Nanoparticles Combined With Photothermal Therapy To Improve Tumor Immunotherapy

Tumor vaccines actively activate the patient’s immune system,amplify tumor-specific T cell responses,and induce sustained immune effects in the body.The low immune response to tumor vaccines is closely related to the low immunogenicity problem and individual differences of tumors.Therefore,it is crucial to solve the above problems for improving the therapeutic effect of tumor vaccines.Here,we designed acid-responsive liposome that can capture antigens and target DCs named PMRL.Subsequently,nanaoparticles cleave the surface liposome membrane to release PMR in slightly acidic environment of the tumor site.Then,tumor associated antigens(TAAs)were generated in situ after photothermal therapy(PTT),and TAAs were precisely captured by PMR to form an in situ vaccine(PMR@pro),which was generated under the synergistic effect of R848.At the same time,due to the surface-modified mannose of PMR,the detection can target the presentation of antigens to DCs and activate their maturation,promoting the cross-presentation of antigens and enhancing the effect of adaptive immunotherapy of tumors.In order to investigate the ability of nanoparticles to capture antigens and stimulate DCs in vitro,we verified the capture of TAAs by the protein adsorption effect and the effect on HMGB-1 after adsorption,and the stimulation effect of antigen-captured nanoparticles on DCs by flow cytometry.Finally,the mouse orthotopic 4T1 breast cancer model was established,the anti-tumor treatment effects of different groups were investigated,and the tumor tissue was analyzed by immunohistochemical staining.Flow cytometry was used to investigate the activation effect of DCs in each group of mice and the results of inducing effector T cells,and immunofluorescence was used to investigate the intratumoral infiltration of CD4~+and CD8~+T cells and the expression of intratumoral CRT.The secretion of interferon-γ,transforming growth factor-β and tumor necrosis factor-α in mouse serum was detected by ELISA kit.The results of blood routine and H&E staining of main organs verified that the PMRL in this design had better biological safety.In order to investigate the long-term immune and memory effects,a mouse model of distant metastatic breast cancer was established 20 days after administration,and the long-term immune memory function of the in situ vaccine was verified from two aspects of tumor recurrence and metastasis.