한빛사 논문
Sejin Sona,b,†, Jutaek Nama,†, Ilia Zenkovb, Lukasz J. Ochyla, Yao Xua, Lindsay Scheetza, Jinjun Shib, Omid C. Farokhzadb,*, James J. Moona,*
aDepartment of Pharmaceutical Sciences and Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States;
bCenter for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States;
*Corresponding Authors
†S.S. and J.N. contributed equally to this work.
Abstract
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 CD8α+ T-cell responses with antitumor efficacy in vivo. The strategy presented in this study is generally applicable for utilizing pathogen-derived molecular patterns for vaccines and immunotherapies.
KEYWORDS : nanoparticle, polysaccharide, mRNA, dendritic cell, vaccine
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