Injectable, Tough Alginate Cryogels as Cancer Vaccines

Abstract

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.

Combining covalent and ionic crosslinking of cryogels results in a tough methacrylated-alginate cryogel with improved injectability in vitro and in vivo. The tough-cryogel-based cancer vaccine generates strong antigen-specific cellular and humoral responses in vivo, and induces potent antibreast cancer prophylactic efficacy in mice. The tough cryogels are a promising minimally invasive delivery platform for cancer vaccinations.

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