(206d) Functionalization of Block Copolymers With Pathogen-Mimicking Sugars for Vaccine Carriers

Biocompatible polymers with controlled architecture such as pentablock copolymers based on pluronic offer sustained gene and drug co-delivery are have been shown to be good candidates as subunit vaccine adjuvants. The temperature and pH dependent micellization and gelation of these pentablock copolymers can provide a depot for immunogens such as protein and gene therapies. The central triblock promotes cellular endocytosis, high gene expression and can activate pro-inflammatory signaling pathways to recruit immune cells. The pentablock copolymer outer blocks condense DNA spontaneously as a result of electrostatic interaction for a sustained combinational therapy. We report the successful atom transfer radical polymerization synthesis of a family of pentablock copolymers. Their ability to form polyplexes with DNA and cytotoxicity profiles were evaluated to determine suitable vaccine candidates. The pentablock copolymers were then functionalized with carbohydrates through an azide-alkyne Huisgen cycloaddition that were characterized and quantified with a phenol sulfuric acid assay, X-ray photoelectron spectroscopy and ζ-potential measurements. Pathogen-associated molecular patterns such as mannose have been shown to activate pattern recognition receptors on antigen presenting cells and enhance the development of a protective immune response.