Engineering the Deformability of Albumin-Stabilized Emulsions for Lymph-Node Vaccine Delivery,Advanced Materials

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Engineering the Deformability of Albumin-Stabilized Emulsions for Lymph-Node Vaccine Delivery
Advanced Materials ( IF 27.4 ) Pub Date : 2021-05-19 , DOI: 10.1002/adma.202100106
Tiantian Song _{1,

2} , Yufei Xia _{2,

3,

4} , Yiqun Du _{2,

5} , Michael W Chen ₆ , Hong Qing ₁ , Guanghui Ma _{2,

3,

4}

Affiliation

A major challenge in vaccine delivery is to achieve robust lymph-node (LN) accumulation, which can capitalize on concentrated immunocytes and cytokines in LNs to stimulate the onset and persistence of adaptive immune responses. Previous attempts at developing vaccine delivery systems have focused on the sizes, charges, or surface ligands but not on their deformability. In fact, the LN homing of antigen-presenting cells depends on deformability to pass through the cellular gaps. Herein, the deformability of albumin-stabilized emulsions is engineered. Owing to self-adaptive deformability, the droplets (≈330 nm) can attach to and deform between cells and adjust their sizes to pass through the endothelial gaps (20–100 nm), favoring direct LN transfer (intercellular pathway). Additionally, owing to relatively large sizes, some emulsions can be retained at the administration sites for potent antigen uptake and activation of APCs as well as LN-targeted delivery of vaccines (intracellular pathway). Compared with solid particles, the dual LN transfer strategy evidently enhances antigen accumulation and activation of LN drainage, potently stimulates cellular immune responses, and increases the survival rate of tumor-bearing mice. Thus, the deformability of albumin-stabilized droplets may offer an efficient strategy for potent LN targeting and enhanced vaccinations.

中文翻译：

设计用于淋巴结疫苗递送的白蛋白稳定乳液的变形能力

疫苗递送的一个主要挑战是实现强大的淋巴结 (LN) 积累，这可以利用 LN 中集中的免疫细胞和细胞因子来刺激适应性免疫反应的发生和持续。以前开发疫苗递送系统的尝试主要集中在尺寸、电荷或表面配体上，而不是它们的变形能力。事实上，抗原呈递细胞的淋巴结归巢取决于通过细胞间隙的变形能力。在此，对白蛋白稳定乳液的可变形性进行了设计。由于自适应变形能力，液滴（约330 nm）可以附着在细胞之间并在细胞之间变形，并调整其大小以穿过内皮间隙（20-100 nm），有利于直接LN转移（细胞间途径）。此外，由于尺寸相对较大，一些乳液可以保留在给药部位，以实现有效的抗原摄取和 APC 的激活以及疫苗的 LN 靶向递送（细胞内途径）。与固体颗粒相比，双重液氮转移策略明显增强了抗原积累和液氮引流激活，有效刺激细胞免疫反应，提高荷瘤小鼠的存活率。因此，白蛋白稳定液滴的可变形性可能为有效的 LN 靶向和增强疫苗接种提供有效的策略。

更新日期：2021-07-02

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