Journal
ADVANCED HEALTHCARE MATERIALS
Volume 7, Issue 10, Pages -Publisher
WILEY
DOI: 10.1002/adhm.201701469
Keywords
alginate; cancer vaccines; injectable; tough cryogels
Funding
- National Institutes of Health [R01 EB015498, R01 DK098055, F32AG057135]
- National Science Foundation Graduate Research Fellowship Program
- Howard Hughes Medical Institute International Student Research Fellowship
- Wyss Institute for Biologically Inspired Engineering
- NATIONAL INSTITUTE ON AGING [F32AG057135] Funding Source: NIH RePORTER
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A covalently crosslinked methacrylated (MA)-alginate cryogel vaccine has been previously shown to generate a potent response against murine melanoma, but is not mechanically robust and requires a large 16G needle for delivery. Here, covalent and ionic crosslinking of cryogels are combined with the hypothesis that this will result in a tough MA-alginate cryogel with improved injectability. All tough cryogels can be injected through a smaller, 18G needle without sustaining any damage, while covalently crosslinked-only cryogels break after injection. Cytosine-phosphodiester-guanine (CpG)-delivering tough cryogels effectively activate dendritic cells (DCs). Granulocyte macrophage colony-stimulating factor releasing tough cryogels recruit four times more DCs than blank gels by day 7 in vivo. The tough cryogel vaccine induces strong antigen-specific cytotoxic T-lymphocyte and humoral responses. These vaccines prevent tumor formation in 80% of mice inoculated with HER2/neu-overexpressing DD breast cancer cells. The MA-alginate tough cryogels provide a promising minimally invasive delivery platform for cancer vaccinations.
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