Engineering polymeric nanocapsules for an efficient drainage and biodistribution in the lymphatic system

Polymer-based nanocarriers have shown potential for enhancing the immunological response of antigens. However, the key drivers for this response have not been fully elucidated. The objective of this work was to evaluate the influence of particle size (≈100 versus 200 nm) and surface composition of polymeric nanocapsules (chitosan, polyarginine and carboxymethyl-β-glucan) on their ability to target specific immune cells in the lymphatics. For this purpose, we used a powerful imaging technique, two-photon intravital microscopy, which minimises tissue damage in the visualisation of biological processes at cellular/subcellular levels. As expected, particle size was critical in the distribution and lymph node accumulation of all nanocapsules. Chitosan particles with a mean size below 100 nm accumulated significantly more in the popliteal lymph node than those with a larger size. Additionally, a comparative analysis of 100 nm nanocapsules with different polymeric shells indicated that cationic nanocapsules (chitosan and polyarginine) show higher accumulation in the popliteal lymph node than the anionic ones (carboxymethyl-β-glucan). In contrast, these anionic nanocapsules showed significant accumulation in the lumbar lymph node. In conclusion, tuning the physicochemical properties and composition of the nanocapsules allows the modulation of their lymphatic uptake and biodistribution, which may have important implications in the immune response.

基于聚合物的纳米载体在增强抗原免疫应答方面展现出应用潜力，但该免疫应答的核心驱动因素尚未完全阐明。本研究旨在评估聚合物纳米胶囊（壳聚糖、聚精氨酸、羧甲基-β-葡聚糖）的粒径（约100 nm与200 nm）与表面组成，对其靶向淋巴管内特定免疫细胞能力的影响。为此，本研究采用了双光子活体显微镜（two-photon intravital microscopy）这一先进成像技术，该技术可在细胞/亚细胞水平可视化生物过程时最大限度减少组织损伤。正如预期，粒径对所有纳米胶囊的体内分布与淋巴结聚集均具有关键影响：平均粒径小于100 nm的壳聚糖纳米颗粒，其在腘淋巴结中的聚集量显著高于粒径更大的组别。此外，对粒径为100 nm、搭载不同聚合物壳层的纳米胶囊的对比分析显示，阳离子纳米胶囊（壳聚糖与聚精氨酸）在腘淋巴结中的聚集量高于阴离子纳米胶囊（羧甲基-β-葡聚糖）；与之相反，此类阴离子纳米胶囊则在腰淋巴结中出现显著聚集。综上，通过调控纳米胶囊的物理化学性质与组成，可实现其淋巴管摄取与体内分布的精准调控，这对抗原免疫应答的优化具有重要意义。