Intelligent nanoparticles loaded simultaneously with anti-PD-L1 and anti-CTLA-4 for photothermal immunotherapy of lung cancer

Abstract

The combination of nanoparticle-based photothermal therapy (PTT) and immunotherapy offers a promising strategy for lung cancer, enabling tumor ablation and the initiation of host immune responses. However, this approach is often hindered by complex treatment protocols and limited immune responses, such as those seen with single immune checkpoint blockade. This study presents a nanoplatform designed for lung cancer PTT combined with immunotherapy, using mesoporous silica nanoparticles (MSNs) as carriers and the photothermal agent PCPDBT, prepared through a straightforward method. The formulated MSNs-PT@PDA-PC exhibit excellent photothermal properties, effectively eliminating primary tumors. Co-loading anti-PD-L1 and anti-CTLA-4 enhances immune functionality. Under laser irradiation, MSNs-PT@PDA-PC facilitates the activation and maturation of dendritic cells, promotes their migration to tumor-draining lymph nodes, and induces a robust antitumor immune response. Impressively, MSNs-PT@PDA-PC combined with PTT successfully eradicated lung cancer, achieving a 60% cure rate, and induced strong immune memory in mice, preventing tumor recurrence and metastasis. This study thus provides a simple and promising synergistic PTT-immunotherapy strategy for effective cancer treatment.