Self-immolative comb-polymers: Multiple-release of side-reporters by a single stimulus event

A new self-immolative polymer based on a polyurethane backbone was developed. The polymer was prepared by simple polymerization of phenylcarbamate monomers, followed by capping of the polymer head with trigger. The polymer head was capped with a trigger designed for removal by penicillin-G amidase (PGA). The enzyme initiates the polymer disassembly to release its reporter units by a single cleavage of the phenylacetamide moiety, followed by 1,6-elimination and decarboxylation reactions. The polymer was incubated in phosphate buffer saline (PBS), pH 7.4, in the presence and in the absence of PGA and the release of 4-nitroaniline was monitored by RP-HPLC. The release of 4-nitroaniline was completed within 6 hours when PGA was added to the polymer solution. Use of drug molecules instead of the reporter units will generate a polymeric drug delivery system that can selectively release a high payload of drug upon simulus by specific enzyme.