Synthesis and Characterization of Clickable Cytocompatible Poly(Ethylene Glycol)-Grafted Polyoxetane Brush Polymers

We report a new family of clickable poly(ethylene glycol) (PEG)-grafted polyoxetane brush polymers as a potential modular platform for delivery of drugs and imaging agents. 3-Ethyl-3-hydroxymethyloxetane (EHMO) monomer reacted with propargyl benzenesulfonate in the presence of sodium hydride to yield alkyne-substituted monomer (EAMO). Subsequently, cationic ring-opening polymerization using boron trifluoride diethyl etherate catalyst and 1,4-butanediol initiator produced P(EAMO) homopolymer with a DP of ∼30 (30 alkynes per chain). Methoxypoly(ethylene glycol) azide (mPEG750-azide) prepared from mPEG750 (750 g mol-1) was grafted to P(EAMO) via copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click chemistry. Water-soluble cytocompatible P(EAMO)-g-PEG brush polymers with controlled degrees of PEGylation were synthesized by varying the feed molar ratio of mPEG750-azide to alkyne (25:100, 50:100, 75:100, and 100:100). 1H NMR, GPC, end-group analysis, FTIR, and DSC were applied for polymer characterization. The utility of P(EAMO)-g-PEG for carrying imaging agents was demonstrated by preparing fluorescently labeled P(EAMO)-g-PEG. 5-(Aminoacetamido)fluorescein (AAF) was used as a model compound. Fluorescein-carrying P(EAMO)-g-PEG was synthesized by click coupling bifunctional spacer 6-azidohexanoic acid (AHA) to P(EAMO)-g-PEG and subsequently coupling of AAF to AHA with EDC/NHS chemistry