Edible exosome-like nanoparticles from Portulaca oleracea L prevent DSS-induced colitis via the promotion of double-positive CD4 + CD8 + T cells

Abstract Plant-derived exosome-like nanoparticles (PDENs) have been paid great attention in the treatment of ulcerative colitis (UC). As a proof of concept, we show that Portulaca oleracea L-derived exosome-like nanoparticles (PELNs) are isolated and identified from edible Portulaca oleracea L with desirable nano-size (~ 160 nm) and a negative zeta potential value (-31.4mV). Moreover, we find that oral administration of PELNs can suppress the expressions of pro-inflammation cytokines (TNF-α, IL-6, IL-12, and IL-1β), and increase the levels of anti-inflammatory cytokine (IL-10) in dextran sulphate sodium (DSS)-induced mice and PHLPP2−/− mice spontaneous colitis contributing to alleviate colitis. Furthermore, orally administered PELNs can display great stability in gastrointestinal tract environment, and specifically targeted to desired inflammatory site in mice colitis. In addition, oral administration of PELNs can effectively maintain the diversity and balance of gut microbiota, and specifically induce the differentiation of double-positive CD4+CD8+T cells (DP CD4+CD8+T cells). In summary, our findings suggest that orally administered PELNs brings a novel and natural colon-targeted agent, and open a new therapeutic avenue in the management of UC.