Design and synthesis of PEGylated amphiphilic block oligomers as membrane anchors for stable binding to lipid bilayer membranes

Abstract

Cell surface engineering is a potentially powerful method for manipulating living cells by decorating the cell membrane with specific molecules. Possible applications include cell therapy, drug delivery systems, bio-imaging, and tissue engineering. The stable binding of synthetic molecules to serve as artificial membrane protein anchors is a promising approach for appending functional molecules to the cell surface. However, such synthetic molecules have previously shown limitations, including cytotoxicity and low cell surface affinity. We synthesized amphiphilic block oligomers, using ruthenium-catalyzed living radical polymerization, as novel membrane anchors for stable binding to lipid bilayer membranes. AB and ABA-type amphiphilic block oligomers were synthesized with poly(ethylene glycol) methacrylate (PEGMA) and varying butyl methacrylate (BMA) contents (PEGMA/BMA ratios of 25/5–25/50). These PEGylated oligomers showed high binding efficiencies (up to 92%) for liposomes, which served as model cell membranes, and low cytotoxicity in K562 cells. Both the BMA content and the block segment sequence in the copolymers strongly affected their binding efficiencies. Oligomers with an ABA-type block structure were much more effective than AB-type block oligomers, random oligomers, or PEGMA homo-oligomers for stable membrane binding. Thus, precise control of the primary structures of the amphiphilic oligomers enabled tuning of their binding efficiencies. These amphiphilic block oligomers hold promise as novel membrane anchors in many biomedical applications. A series of amphiphilic block oligomers were designed and synthesized using ruthenium-catalyzed living radical polymerization with poly(ethylene glycol) and butyl methacrylates (BMA). These PEGylated oligomers showed high binding efficiencies for liposomal preparations as model cell membranes, and also had low cytotoxicity. BMA contents and monomer sequences in the copolymers strongly affected their binding efficiencies. Current method enabled precise control of the primary structures of amphiphilic oligomers, allowing tuning of their binding efficiencies. These amphiphilic block oligomers have promise as novel membrane anchors for many biomedical applications.