The Effect of Size and Charge of Lipid Nanoparticles Prepared by Microfluidic Mixing on Their Lymph Node Transitivity and Distribution
The Effect of Size and Charge of Lipid Nanoparticles Prepared by Microfluidic Mixing on Their Lymph Node Transitivity and Distribution
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DOI：
10.1021/acs.molpharmaceut.9b01182
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发表时间：
2020-03-01
影响因子：
4.9
通讯作者：
Harashima, Hideyoshi
中科院分区：
文献类型：
--
作者：
Nakamura, Takashi;Kawai, Minori;Harashima, Hideyoshi
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抗原和佐剂等免疫功能分子输送到LN是实现免疫反应有效结果的有效策略。递送系统的大小和电荷在很大程度上影响到LN的传递性和在LN内的分布。尽管微流控混合法制备的pH敏感脂质纳米粒(LNPs)是最新的临床应用系统，但其大小和电荷对LN的传递性和分布的影响目前尚不清楚。我们研究了微流控混合法制备的LNPs的尺寸和电荷效应对LNS的传递性和分布的影响。30 nm大小的LNP(30-LNP)可以有效地转运到LNS并被CD8(+)树突状细胞摄取，而100和200 nm大小的LNP的效率显著降低。此外，中性、正电和负电的30-LNP之间的比较研究表明，负的30-LNP比其他LNP更有效地向LN移动。有趣的是，30-LNP的负值到达了大脑皮层深处，即T细胞区。我们的发现为设计微流控混合法制备的LN靶向LNPs和纳米颗粒在LNS中的移位提供了有益的启示。
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.