A Single Enzyme Mediates the "Quasi-Living" Formation of Multiblock Copolymers with a Broad Biomedical Potential

• Published in: Biomacromolecules Vol. 21; no. 6; pp. 2132 - 2146
• Main Authors: Scheibel, Dieter Michael, Guo, Dandan, Luo, Juntao, Gitsov, Ivan
• Format: Journal Article
• Language: English
• Published: United States 08.06.2020
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/acs.biomac.0c00126

This study describes a unique "quasi-living" block copolymerization method based on an initiation by a single enzyme. We use this term to describe a process where a preformed polymer chain can be reactivated to continue propagating with a second or third comonomer without addition of new catalyst. The presented strategy involves a laccase (oxidoreductase) mediated initial polymerization of 4-hydroxyphenylacetic acid to a homopolymer containing phenolic terminal units, which in turn can be easily reactivated by the same enzyme in the same reaction vessel to continue propagation with a second monomer (tyramine). Increased copolymer yield (up to 26.0%) and polymer molecular mass (up to = 116 000 Da) are achieved through the addition of previously developed micellar and hydrogel enzyme complexing agents. The produced poly(tyramine)- -poly(4-hydroxyphenylacetic acid)- -poly(tyramine) is water-soluble and able to self-assemble in aqueous solution. Both tyramine blocks were successfully modified with ibuprofen moieties (up to 24.6% w/w load) as an example for potential polymer drug conjugation. The copolymerization could be further extended with addition of a third (fluorescent) comonomer in the same reaction vessel to yield a fluorescent pentablock copolymer. The successful modifications and advantageous solution behavior of the produced copolymers demonstrate their viability as versatile drug delivery and/or bioimaging agents, as confirmed by cytotoxicity and cellular uptake studies.