Journal
ACS NANO
Volume 4, Issue 2, Pages 1178-1186Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn901478z
Keywords
nanomedicine; fullerene; dendritic cells; activation; Th1 polarization
Categories
Funding
- National Cancer Institute, National Institutes of Health [NO1-CO-12400]
- NSFC [30772529]
- China MOST 973 projects [2010CB933900]
- Tianjin Commission of Science and Technology [08ZCKFSH04800]
- U.S. National Foundation of Cancer Research
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Dendritic cells play a pivotal role in host immune defense, such as elimination of foreign pathogen and inhibition of tumorigenesis. In this paper, we report that [Gd@C-82(OH)(22)](n) could induce phenotypic maturation of. dendritic cells by stimulating DC production of cytokines including IL-12p70, upregulating DC co-stimulatory (CD80, CD83, and CD86) and MHC (HLA-A,B,C and HLA-DR) molecules, and switching DCs from a CCL5-responsive to a CCL19-responsive phenotype. We found that [Gd@C-82(OH)(22)](n) can induce dendritic cells to become functionally mature as illustrated by their capacity to activate allogeneic T cells. Mice immunized with ovalbumin in the presence of [Gd@C-82(OH)(22)](n) exhibit enhanced ovalbumin-specific Th1-polarized immune response as evidenced by the predominantly increased production of IFN gamma, IL-1 beta, and IL-2. The [Gd@C-82(OH)(22)](n) nanoparticle is a potent activator of dendritic cells and Th1 immune responses. These new findings also provide a rational understanding of the potent anticancer activities of [Gd@C-82(OH)(22)](n) nanoparticles reported previously.
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