Journal
POLYMER CHEMISTRY
Volume 4, Issue 8, Pages 2464-2469Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3py00085k
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Funding
- National Institutes of Health [R21 CA 137506-01]
- Army Research Office [57858CH]
- National Science Foundation for support through the Center for Hierarchical Manufacturing at UMass Amherst [CMMI-0531171]
- National Science Foundation [DGE-0707424]
- IGERT program through the Institute for Cellular Engineering at UMass Amherst
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The covalent conjugation of bovine serum albumin (BSA) to disulfide cross-linked polymeric nanogels is reported. Polymeric nanogel precursors were synthesized via a reversible addition-fragmentation chain transfer (RAFT) random copolymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA) and pyridyl disulfide methacrylate (PDSMA). Reaction of the p(PEGMA-co-PDSMA) with dithiothreitol resulted in the formation of nanogels. PDSMA serves as both a crosslinking agent and a reactive handle for the surface modification of the nanogels. Lipophilic dye, DiI, was sequestered within the nanogels by performing the crosslinking reaction in the presence of the hydrophobic molecule. Thiol-enriched BSA was conjugated to nanogels loaded with DiI via a thiol-disulfide exchange reaction between the BSA and the surface exposed nanogel pyridyl disulfides. Conjugation was confirmed by fast protein liquid chromatography, dynamic light scattering, and agarose and polyacrylamide gel electrophoresis. We expect that this methodology is generally applicable to the preparation of nanogel-protein therapeutics.
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