Journal
NANO LETTERS
Volume 20, Issue 3, Pages 1499-1509Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.9b03483
Keywords
nanoparticle; polysaccharide; mRNA; dendritic cell; vaccine
Categories
Funding
- NIH [R01EB022563, R01AI127070, R01CA210273, R01CA223804, U01CA210152]
- MTRAC for Life Sciences Hub
- Emerald Foundation
- David Koch-Prostate Cancer Foundation Award in Nanotherapeutics
- Melanoma Research Alliance [348774]
- DoD/CDMRP Peer Reviewed Cancer Research Program [W81XWH-16-1-0369]
- NSF CAREER Award [1553831]
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Innate immune cells recognize and respond to pathogen-associated molecular patterns. In particular, polysaccharides found in the microbial cell wall are potent activators of dendritic cells (DCs). Here, we report a new class of nanocapsules, termed sugar-capsules, entirely composed of polysaccharides derived from the microbial cell wall. We show that sugar-capsules with a flexible polysaccharide shell and a hollow core efficiently drain to lymph nodes and activate DCs. In particular, sugar-capsules composed of mannan (Mann-capsule) carrying mRNA (mRNA) promote strong DC activation, mRNA translation, and antigen presentation on DCs. Mann-capsules elicit robust antigen-specific CD4+ and CD8 alpha+ P reca, T-cell responses with antitumor efficacy in vivo. The strategy presented in this study Y is generally applicable for utilizing pathogen-derived molecular patterns for vaccines and immunotherapies.
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