Highly triple-effective synergy based on tetrahedral DNA nanostructure-induced tumor vaccines for cancer therapy
Jianqin Yan, Hongli Yu, Xiaowen Tang, Fashun Li, Zhipeng Li, Yan Liang, Bin He, Xianwen Wang, Yong Sun
Abstract
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.