期刊
MOLECULAR PHARMACEUTICS
卷 17, 期 3, 页码 944-953出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.9b01182
关键词
nanoparticle; lymph node; microfluidic; particle size; particle charge; pH-sensitive lipid; T cell
资金
- JSPS KAKENHI [17H03974]
- JST CREST (Japan) [JPMJCR17H1]
- Japan Agency for Medical Research and Development (AMED)
- Hokkaido University
- Pharma Science Open Unit (PSOU) - MEXT under Support Program for Implementation of New Equipment Sharing System
- Global Facility Center (GFC)
- Grants-in-Aid for Scientific Research [17H03974] Funding Source: KAKEN
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.
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