An Orthogonal Click-Chemistry Approach to Design Poly(glycerol monomethacrylate)-based Nanomaterials for Controlled Immunostimulation

作者：Ragupathy Lakshminarayanan; Millar Douglas G; Tirelli Nicola; Cellesi Francesco^*

来源：Macromolecular Bioscience, 2014, 14(11): 1528-1538.

DOI：10.1002/mabi.201400146

• adjuvants
• dendritic cells
• immunostimulation
• mannose
• poly(glycerol monomethacrylate)

A versatile approach is proposed for the synthesis of novel immunoactive nanomaterials based on biocompatible poly(glycerol monomethacrylate) (PGMMA). Propargyl-terminated PGMMA is synthesized via atom transfer radical polymerization and then modified through the introduction of dangling acrylate groups, at controlled degree of functionalisation. Acrylates are then able to react quantitatively with thiols, such as immunoactive thiomannose, through Michael-type addition under mild conditions and at a physiologically acceptable pH. The terminal propargyl group can be modified independently with azide end-capping groups and it is utilized to graft the macromolecules to a fluorescent dye. The resulting mannose-linked PGMMAs confirm a safe cytotoxic profile and are able to stimulate cytokine production (TNF alpha), membrane protein expression (CD40), and cellular uptake in bonemarrow derived dendritic cells. Cell stimulation is dependent on the mannose content and enhanced by serum proteins, suggesting a role for mannose-binding receptors and/or complement receptors in the cell membrane.

• 出版日期2014-11