Abstract
The conjugation of hydrophilic polymers to proteins is an effective approach to prolonging their circulation time in the bloodstream and, hence, improving their delivery to the target region of interest. In this work, we report the synthesis of protein-polymer conjugates using a highly water-soluble sulfoxide-containing polymer, poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA), through a combination of "grafting-to" and "grafting-from" methods. Oligomeric MSEA was synthesized by conventional reversible addition-fragmentation chain transfer (RAFT) polymerization and subsequently conjugated to lysozyme to produce a macromolecular chain transfer agent. This was followed by a visible light-mediated chain extension polymerization of MSEA to obtain a lysozyme-PMSEA conjugate (Lyz-PMSEA). It was found that the Lyz-PMSEA conjugate exhibited much reduced macrophage cellular uptake compared with unmodified and PEGylated lysozyme. Moreover, the Lyz-PMSEA conjugate was able to circulate longer in the bloodstream, demonstrating significantly improved pharmacokinetics demanded for pharmaceutical applications.
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