Highly triple-effective synergy based on tetrahedral DNA nanostructure-induced tumor vaccines for cancer therapy

Chemotherapy (CT) can convert tumor cells into “tumor vaccines” through immunogenic cell death (ICD). However, the antitumor immunity elicited by CT-induced tumor vaccines is weak. Therefore, developing efficient CT-induced tumor vaccines is a challenge. Herein, we report a novel strategy to induce CT with a strong immunogenic effect. Targeted tetrahedral DNA nanostructures modified by AS1411 and immune adjuvant CpG (abbreviation: ACT) were used to achieve a multi-drug co-loading system of DOX and methylene blue (MB, photosensitizer for photodynamic therapy), ACT-loaded DOX and MB (ACT@DM), for multi-mode and combined chemo-photo-immune therapy. ACT@DM effectively generated reactive oxygen species and promoted cellular uptake through photochemical internalization, showing an excellent antitumor effect. Furthermore, ACT@DM induced a significant ICD effect under light irradiation, activated immune cells, and promoted the maturation of dendritic cells and secretion of related cytokines, thereby resulting in the activation and infiltration of T lymphocytes. The combination of CT-photo-immune therapy significantly enhanced the proportions of cytotoxic T cells (CD8+ CTL) and CD8+ CTL/regulatory T cells, indicating effective activation of T cells and improvement of immunosuppression, which cooperatively inhibited tumor growth. This study provides a simple but effective strategy for exploring antitumor immunotherapy, achieving high-efficiency T cell activation, and multimodal combination therapy.