Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Division of Applied Chemistry, Faculty of Engineering, Hokkaido University, Kita-13, Nishi-8, Kita-Ku, Sapporo 060-8628, Japan.
Mol Pharm. 2020 Mar 2;17(3):944-953. doi: 10.1021/acs.molpharmaceut.9b01182. Epub 2020 Feb 5.
Because the lymph node (LN) is a critical organ for inducing immune responses against pathogens and cancers, the transport of immune functional molecules such as antigens and adjuvants to LNs by delivery systems is a useful strategy for the effective outcome of an immune response. The size and charge of a delivery system largely affect the transitivity to and distribution within LN. Although pH-sensitive lipid nanoparticles (LNPs) prepared by microfluidic mixing are the latest delivery system to be applied clinically, the effects of their size and charge on the transitivity to and distribution within LN are currently unknown. We investigated the size and charge effect of LNPs prepared by microfluidic mixing on transitivity to and distribution within LNs. A 30 nm-sized LNP (30-LNP) was efficiently translocated to LNs and was taken up by CD8 dendritic cells, while the efficiency was drastically decreased in the cases of 100 and 200 nm-sized LNPs. Furthermore, a comparative study between neutral, positively, and negatively charged 30-LNP revealed that the negative 30-LNP moved to the LN more efficiently than the other LNPs. Interestingly, the negative 30-LNP reached the deep cortex, namely, the T cell zone. Our findings provide informative insights for designing LN-targeting LNPs prepared by microfluidic mixing and for the translocation of nanoparticles in LNs.
由于淋巴结（LN）是诱导针对病原体和癌症的免疫反应的关键器官，因此通过递送系统将免疫功能分子（如抗原和佐剂）输送到 LN 是有效引发免疫反应的有用策略。递送系统的大小和电荷在很大程度上影响其向 LN 的通透性和在 LN 内的分布。尽管通过微流控混合制备的 pH 敏感脂质纳米颗粒（LNPs）是最新应用于临床的递送系统，但目前尚不清楚其大小和电荷对向 LN 的通透性和在 LN 内的分布的影响。我们研究了通过微流控混合制备的 LNPs 的大小和电荷对向 LN 的通透性和在 LN 内分布的影响。30nm 大小的 LNP（30-LNP）能够有效地向 LN 转运，并被 CD8 树突状细胞摄取，而 100nm 和 200nm 大小的 LNP 的效率则明显降低。此外，对中性、正电荷和负电荷的 30-LNP 进行的比较研究表明，负电荷的 30-LNP 比其他 LNP 更有效地向 LN 转运。有趣的是，负电荷的 30-LNP 到达了深部皮质，即 T 细胞区。我们的研究结果为设计通过微流控混合制备的靶向 LN 的 LNPs 以及纳米颗粒在 LN 中的转运提供了有价值的见解。
