Polydopamine-based nanoplatform for photothermal ablation with long-term immune activation against melanoma and its recurrence

The high risk of tumor recurrence presents a big challenge in melanoma therapy. Photothermal therapy (PTT) has merged as a powerful weapon against tumor in recent years, which produces tumor-associated antigens (TAA) and recruits dendritic cells (DCs) to tumor sites through immunogenic cell death (ICD) for immune activation. However, due to the lack of activation signals of DCs, the immune effect induced by PTT is not sufficient to inhibit the recurrence and proliferation of tumor. To efficiently cooperate PTT and immunotherapy to circumvent tumor recurrence, here we constructed a polydopamine (PDA) based core-shell nanoplatform loading CpG ODNs to elicit robust photothermal ablation and antitumor immune responses. Cationized polydopamine coated with hyaluronic acid (HA) shell was proven an efficient photothermal agent that increased the surface temperature of tumor by 16 °C and induced ICD. CpG ODNs effectively induced maturation of DCs by elevating the expression of co-stimulating markers. PTT combined with CpG ODNs achieved a remarkable synergistic treatment effect in the maturation of DCs and activation of T cells in melanoma-bearing mice model compared with PTT or CpG ODNs alone. Furthermore, in a tumor recurrence model, photothermal-immune combination therapy increased the infiltration of CTLs in distant tumor compared with PTT or CpG ODNs alone. The combination therapy overcame insufficient immunity at distant tumor caused by PTT alone and relieved immunosuppression microenvironment of the tumor. Hence, the PDA based core-shell nanoplatform presents a potent photo-immunotherapy against proliferation and recurrence of melanoma. STATEMENT OF SIGNIFICANCE: In order to solve the insufficient immunity induced by photothermal therapy (PTT), CpG ODNs were utilized to enhance the weak immune response mediated by PTT through inducing DCs maturation. Hence, we designed a polydopamine (PDA) based core-shell nanoplatform loading CpG ODNs followed by hyaluronic acid named PPP/CpG/HA to elicit robust photothermal ablation and antitumor immune responses. CpG ODNs were delivered to the tumor site through the targeting effect of the HA shell. The core-shell nanoplatform achieved a remarkable synergistic treatment effect in the maturation of DCs and activation of T cells, thereby overcoming insufficient immunity at distant tumor caused by PTT alone. The core-shell nanoplatform presents a potent photo-immunotherapy against proliferation and recurrence of melanoma.