Second Near-infrared Imaging-guided Tumor Chemotherapy-photothermotherapy Combined With Immune Checkpoint

Malignant tumors are one of the major diseases that threaten human life.Current conventional tumor treatment methods include surgical resection,chemotherapy,molecular targeted therapy and radiotherapy.However,the efficacy of these conventional treatment methods is still limited,and the development of new treatment strategies is urgently needed.In recent years,following conventional treatment methods,some other treatment techniques have gradually emerged.In terms of physical therapy,the new minimally invasive anti-cancer technology"photothermal therapy"has the advantage of local treatment,non-invasive,controllable radiation and temperature.In terms of immunotherapy,based on its own immune system,the use of immune checkpoint blockade methods to promote the proliferation of tumor-infiltrating CD8~+T lymphocytes becomes more and more popular.The study found that oxaliplatin combined with photothermal therapy can induce immunogenic death(ICD)of tumor cells and enhance the effect of tumor immune response,but at the same time,tumor cells will have their own defense mechanisms,and the surface will express PD-L1 highly Thereby inducing apoptosis of CTLs.By combining the immune checkpoint inhibitor Anti-PD-L1 antibody,it can avoid the inactivation and even apoptosis of CTLs,effectively relieve the tumor immunosuppressive environment and inhibit tumor growth.In this paper,the nano-drug loading system of amphiphilic polymer prodrug PBOXA and two-region small molecule probe was first constructed.Nanoparticles can effectively accumulate on the tumor site based on the EPR effect.The small-molecule probe realizes imaging with high signal-to-noise ratio in the near-infrared two-region window under the loading of nanoparticles,and exhibits good photothermal properties.In this system,near-infrared two-zone imaging guides precise photothermal therapy.Chemo-photothermal induces ICD in tumor cells,improves tumor immunogenicity,activates anti-tumor immune response,and promotes the infiltration of CTLs.Interrupt the PD-1/PD-L1 pathway and resolve the suppression state of the tumor immune system.By means of second near-infrared imaging,we observed the accumulation and distribution of nanoparticles in the tumor site of the CT26 colon cancer tumor-bearing mouse model.Chemotherapy-photothermal therapy combined with Anti-PD-L1 antibody treatment significantly promoted the maturation of DCs,the infiltration of CTLs in T lymphocytes in tumors,and inhibited the growth of tumors,or even completely eliminated tumors.The triple combination of chemotherapy,photothermal and immune checkpoint blockade provides a new therapeutic direction for tumor immunotherapy.