Current efforts to develop novel vaccine nanotechnologies to increase cytotoxic T lymphocytes have met the challenges of the limited efficacy of antigen cross-presentation. Recent studies have uncovered a unique biological mechanism by which activation of the NADPH oxidase 2 (NOX2) complex, a major source of reactive oxygen species (ROS), enhances the cross-presentation by antigen-presenting cells (APCs). Inspired by the NOX2 mechanism, we devise biomineralized nanovaccines named NVs^cp, which are developed by in situ growth of calcium peroxide on nanovaccines self-assembled with the model antigen ovalbumin. The ~80 nm NVs^cp efficiently flow to the draining lymph nodes, where they accumulate within APC endo-/lysosomes, and generate a rapid burst of ROS in response to the acidic endo-/lysosomal environment with the subsequent endo-/lysosomal lipid peroxidation. Accompanied by the process, NVs^cp stimulate distinct APCs maturation and antigen presentation to T lymphocytes. Notably, high levels of antigen-specific CD8⁺ T cell responses, accompanied by the induction of CD4⁺ T helper cells, are achieved. More importantly, NVs^cp significantly increase the ratios of intratumoral CD8⁺ T/regulatory T cells and achieve prominent tumor therapy effects. The NOX2-inspired biomineralized NVs^cp represent an effective and easily applicable strategy that enables the strong cross-presentation of exogenous vaccine antigens.

目前开发新型疫苗纳米技术以增加细胞毒性T 淋巴细胞的努力已经遇到了抗原交叉呈递效力有限的挑战。最近的研究揭示了一种独特的生物学机制，通过该机制，活性氧 (ROS) 的主要来源 NADPH 氧化酶 2 (NOX2) 复合物的激活增强了抗原呈递细胞 (APC) 的交叉呈递。受 NOX2 机制的启发，我们设计了名为 NVs ^{cp 的}生物矿化纳米疫苗，该疫苗是通过在与模型抗原卵清蛋白自组装的纳米疫苗上原位生长过氧化钙而开发的。~80 nm NVs ^cp有效地流向引流淋巴结，它们在 APC 内/溶酶体中积累，并产生快速爆发的 ROS 以响应酸性内/溶酶体环境以及随后的内/溶酶体脂质过氧化。伴随着这个过程，NVs ^cp刺激不同的 APCs 成熟和抗原呈递给 T 淋巴细胞。值得注意的是，实现了高水平的抗原特异性 CD8 ⁺ T 细胞反应，伴随着 CD4 ⁺ T 辅助细胞的诱导。更重要的是，NVs ^cp显着增加了肿瘤内 CD8 ⁺ T/调节性 T 细胞的比例，并取得了显着的肿瘤治疗效果。受 NOX2 启发的生物矿化 NVs ^cp 代表了一种有效且易于应用的策略，可以实现外源疫苗抗原的强交叉呈递。