Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen University, Shenzhen 518035, China; Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen University, Shenzhen 518035, China.
J Control Release. 2022 May;345:601-609. doi: 10.1016/j.jconrel.2022.03.048. Epub 2022 Mar 25.
During vaccine delivery in vivo, the vaccine carrier dynamically adsorbs the surrounding proteins or biomacromolecules to form a protein corona layer, which determines the physiological and therapeutic responses of the vaccine. Although the importance of the protein corona effect in drug delivery is widely accepted, understanding of the rational use of the protein corona to improve antigen controlled release is still sparse. Here, we constructed a protein corona-driven nanovaccine (PCNV), which has the dual effects of resisting the protein corona-induced antigen extracellular release and promoting protein corona-triggered antigen cytosolic release under reductive conditions. Specifically, the nanovaccine was formulated via the assembly of fluorinated dendrigraft-poly-lysine and cleavable antigen-CpG conjugate. Before entering antigen-presenting cells (APCs), the anchoring effect of CpG was used to avoid the dissociation of antigens from the carrier even under the protein corona effect. While nanovaccine enters the APCs, the intracellular reducing conditions can induce a break in the disulfide bond between CpG and antigen. Notably, at the same time, the intracellular protein corona effect triggers antigen release from the carrier and achieves efficient antigen presentation. In addition, the PCNV produced a significant prophylactic and therapeutic antitumor response in the mouse model. Therefore, the rational use of the protein corona effect provides an effective strategy for vaccine delivery.
在体内疫苗传递过程中，疫苗载体动态吸附周围的蛋白质或生物大分子形成蛋白质冠层，这决定了疫苗的生理和治疗反应。尽管蛋白质冠效应在药物传递中的重要性已被广泛接受，但对于合理利用蛋白质冠来改善抗原控制释放的理解仍然很少。在这里，我们构建了一种蛋白质冠驱动的纳米疫苗（PCNV），它具有抵抗蛋白质冠诱导的抗原细胞外释放和在还原条件下促进蛋白质冠触发的抗原细胞质释放的双重作用。具体来说，纳米疫苗是通过氟化树枝状大分子聚赖氨酸和可裂解抗原-CpG 缀合物的组装形成的。在进入抗原呈递细胞（APCs）之前，CpG 的锚定作用被用于避免抗原从载体解离，即使在蛋白质冠效应下也是如此。而当纳米疫苗进入 APCs 时，细胞内的还原条件会导致 CpG 与抗原之间的二硫键断裂。值得注意的是，与此同时，细胞内的蛋白质冠效应触发了载体中抗原的释放，并实现了有效的抗原呈递。此外，PCNV 在小鼠模型中产生了显著的预防性和治疗性抗肿瘤反应。因此，合理利用蛋白质冠效应为疫苗传递提供了一种有效的策略。
