Nanovaccine biomineralization for cancer immunotherapy: a NADPH oxidase-inspired strategy for improving antigen cross-presentation via lipid peroxidation
Nanovaccine biomineralization for cancer immunotherapy: a NADPH oxidase-inspired strategy for improving antigen cross-presentation via lipid peroxidation
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用于癌症免疫治疗的纳米疫苗生物矿化：一种受 NADPH 氧化酶启发的策略，通过脂质过氧化改善抗原交叉呈递
DOI：
10.1016/j.biomaterials.2021.121089
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发表时间：
2021-09-01
期刊：
影响因子：
14
通讯作者：
Li, Yongyong
中科院分区：
文献类型：
--
作者：
Su, Runping;Chong, Gaowei;Li, Yongyong
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满足了抗原交叉呈递的有限效力的挑战。最近的研究发现了一种独特的生物学机制，通过激活NADPH氧化酶2(NOX2)复合体来增强抗原提呈细胞(APC)的交叉递呈。NOX2是ROS的主要来源。受NOX2机制的启发，我们设计了生物矿化纳米疫苗NVS(Cp)，它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。类似于80 nm的Nvs(Cp)有效地流向引流淋巴结，在那里它们聚集在APC内切/溶酶体中，并在酸性内切/溶酶体环境中产生快速爆发的ROS，随后发生内切/溶酶体脂质过氧化。伴随着这一过程，Nvs(Cp)刺激不同的APC成熟并将抗原递呈给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，并伴随着CD4(+)T辅助细胞的诱导。更重要的是，NVS(Cp)显著提高了肿瘤内CD8(+)T细胞/调节性T细胞的比例，取得了显著的肿瘤治疗效果。受NOX2启发的生物矿化NVS(Cp)是一种有效且易于应用的策略，能够实现外源疫苗抗原的强烈交叉呈递。
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 similar to 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.