Ramulus mori polysaccharide (RMP),
one of the most important active components of R. mori, has been attracting increasing interest because of its potent bioactive
properties, including anti-inflammatory, antitumor, and antidiabetic
effects. Despite the great therapeutic potential of RMP, its inherent
properties of low bioavailability and brief biological half-life have
limited its applications to the clinic. Thus, RMP was packaged by
poly(lactic-co-glycolic acid) (PLGA) nanoparticles
to develop a novel anti-inflammatory nanomedicine (PLGA-RMP) in this
study. The nanoparticles were synthesized via a double-emulsion solvent
evaporation technique, and the average diameter of PLGA-RMP was about
202 nm. PLGA-RMP nanoparticles reduced the expression of inflammatory
cytokines while promoting the production of IL-10, and boosted the
phenotypic shift in macrophages in vitro. Furthermore, lipopolysaccharide
(LPS)-induced inflammatory bowel disease (IBD) in mouse was used to
examine the anti-inflammatory effect of PLGA-RMP in vivo. Oral administration
of PLGA-RMP in LPS-induced IBD mice substantially mitigated the intestinal
inflammation compared to treatment with LPS alone, as evidenced by
attenuation of disease activity index scores and inflammatory damage
in the intestine. Meanwhile, PLGA-RMP suppressed the expression and
secretion of specific inflammatory cytokines including TNF-α,
IL-6, IL-1β, and PGE2 in the inflamed intestine while inhibiting
the activation of CD3+CD8+ T-cells and increasing
the number of activated Tregs in the intestine. These results
indicated that PLGA-RMP deserves further consideration as a potential
therapeutic nanomedicine to treat various inflammatory diseases, including
IBD.
Clinical management of chronic hepatitis B (CHB) virus infection remains a big challenge and urges the development of novel therapeutics to achieve long-term virological control and seroconversion. In this study, we report on the development and evaluation of a highly efficacious therapeutic mRNA vaccine encoding the full-length hepatitis B virus (HBV) surface antigen (HBsAg). In pAAV-HBV1.2 and rAAV8-HBV1.3-transduced CHB mouse models, the HBV mRNA vaccine demonstrated potent therapeutic efficacy indicated by a complete serum viral clearance, a remarkable decline in intrahepatic HBcAg, viral DNA and RNA copies, as well as the induction of robust levels of anti-HBs antibodies, virus-specific T cells and memory B cells. In addition, the HBV mRNA vaccine induced strong innate immune activation, represented by the maturation of CD8α+ and CD103+ cDC1, CD11b+ cDC2, monocytes and neutrophils. Taken together, the HBV mRNA vaccine is a promising therapeutic candidate holding prospect for further development and clinical investigation.
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