Robust Nanovaccine Based on Polydopamine‐Coated Mesoporous Silica Nanoparticles for Effective Photothermal‐Immunotherapy Against Melanoma

Abstract Nanoparticle‐based combination therapy strategy of photothermal therapy (PTT) and immunotherapy is an attractive cancer treatment for ablating tumors and eliciting host immune responses. However, this strategy is often hampered by tedious treatment process and limited immune response, and usually needs to be combined with checkpoint blockades to enhance therapeutic effect. Herein, a nanoplatform with mesoporous silica nanoparticles (MSNs) as a vector, which integrated photothermal agent polydopamine (PDA), model antigen ovalbumin (OVA), and antigen release promoter ammonium bicarbonate (ABC) in an easy way for melanoma PTT‐immunotherapy is designed. The formulated MSNs‐ABC@PDA‐OVA nanovaccine exhibits excellent photothermal properties and effectively eliminates primary tumors. Under laser irradiation, the MSNs‐ABC@PDA‐OVA nanovaccine realizes rapid antigen release and endosome escape, enhances dendritic cells activation and maturation, facilitates migration to tumor‐draining lymph nodes, and induces robust antitumor immune responses. Impressively, single injection of MSNs‐ABC@PDA‐OVA combines with single round of PTT successfully eradicates melanoma tumors with a cure rate of 75% and generates strong immunological memory to inhibit tumor recurrence and lung metastasis. Hence, the research offers a simple and promising strategy of synergistic PTT‐immunotherapy to effectively treat cancer.