Journal
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
Volume 21, Issue -, Pages 199-208Publisher
CELL PRESS
DOI: 10.1016/j.omtm.2021.03.006
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology (Tokyo, Japan) [S1511011]
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Extracellular vesicles derived from mammalian cells have potential as carriers for drug delivery systems, but there are still challenges to be overcome for clinical applications. In this study, acerola exosome-like nanoparticles were explored for orally administered nucleic acid drug delivery, showing successful encapsulation of miRNA and downregulation of target genes. Oral delivery of AELNs was effective in transferring small RNA to the digestive system, with peak gene-suppressing effects observed in the small intestine and liver 1 day post-administration.
Extracellular vesicles derived from mammalian cells could be useful carriers for drug delivery systems (DDSs); however, with regard to clinical application, there are several issues to be overcome. Acerola (Malpighia emarginata DC.) is a popular health food. In this study, the feasibility of orally administered nucleic acid drug delivery by acerola exosome-like nanoparticles (AELNs) was examined. AELNs were recovered from acerola juice using an affinity column instead of ultracentrifugation. MicroRNA (miRNA) was sufficiently encapsulated in AELNs by 30-min incubation on ice and was protected against RNase, strong acid, and base treatments. The administration of an AELN/miRNA mixture in cells achieved downregulation of the miRNA's target gene, and this mixture showed cytoplasmic localization. AELNs orally delivered small RNA to the digestive system in vivo. The target gene-suppressing effect in the small intestine and liver peaked 1 day after administration, indicating potential for use as an oral DDS for nucleic acid in the digestive system.
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