Low-Temperature PTT Combined With Immune Modulator For Malignant Tumor Treatment

In recent years,tumor immunotherapy has shown great potential,there are still many defects in several aspects,such as: Lack of tumor-associated antigen;Insufficient antigen presenting ability of antigen presenting cells and impaired T lymphocyte response;The inhibitory effect of immunosuppressive cells in the tumor microenvironment.In fact,the current immunotherapy was difficult to achieve a satisfactory therapeutic effect,and more strategies should be needed to address the limitations of immunotherapy.To overcome these obstacles,a cascade synergistic immunotherapy nano-system(denoted as CpG@PDA-FA)was designed to elevate anti-cancer immune response.The combination nano-system including a photothermal agent polydopamine(PDA)and immuno-modulator CpG oligodeoxynucleotides(CpG ODNs).On the one hand,PDA was served as a photothermal agent to induce low temperature PTT.It lead to immunogenic cell death(ICD),a programmed cell death pathway,which can activate DCs and enhance anti-tumor immune response of T cells.On the other hand,CpG ODNs further promoted maturation and migration of DCs as well as ameliorates immunosuppression microenvironment of tumor(TME).CpG@PDA-FA NPs provided bidirectional immunotherapy to enhance tumor immunogenicity and reshape immune microenvironment for tumor suppression,which embodied the cascades therapeutic effect of low-temperature PTT and immunotherapy.The results showed that :(1)CpG@PDA-FA NPs has good tumor targeting and biosafety.Compared with the low-temperature PTT group or the CpG group alone,the synergistic antitumor effect of photothermal immunity mediated by CpG@PDA-FA NPs group was better.In this group,obvious tumor growth inhibition was observed.Tumor volume and weight were significantly reduced after treatment,and the mean survival time of mice was significantly prolonged.(2)Immunogenic death of tumor cells was successfully induced by low temperature hyperthermia mediated by CpG@PDA-FA NPs,which was characterized by increased ectropion of calreticulin and increased release of adenosine triphosphate and high migration group protein B1.These signaling molecules were beneficial to the activation of anti-tumor immunity.(3)Combined photothermal immunotherapy mediated by CpG@PDA-FA NPs reshaped the tumor microenvironment and alleviated immunosuppression.After treatment,the number of mature DCs and activated T cells in the tumor microenvironment increased,while the number of regulatory T cells and myeloid suppressor cells decreased.