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An Orthogonal Click‐Chemistry Approach to Design Poly(glycerol monomethacrylate)‐based Nanomaterials for Controlled Immunostimulation
Author(s) -
Ragupathy Lakshminarayanan,
Millar Douglas G.,
Tirelli Nicola,
Cellesi Francesco
Publication year - 2014
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201400146
Subject(s) - propargyl , chemistry , mannose , atom transfer radical polymerization , biochemistry , click chemistry , biophysics , acrylate , polymer chemistry , polymerization , organic chemistry , polymer , monomer , biology , catalysis
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 (TNFα), membrane protein expression (CD40), and cellular uptake in bone marrow 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.