Impact of the polymer backbone chemistry on interactions of amino-acid-derived zwitterionic polymers with cells  

作　　者：Meike N.Leiske Bruno G.De Geest Richard Hoogenboom 

机构地区：[1]Supramolecular Chemistry Group,Centre of Macromolecular Chemistry(CMaC),Department of Organic and Macromolecular Chemistry,Ghent University,Krijgslaan 281 S4,B-9000,Ghent,Belgium [2]Department of Pharmaceutics and Cancer Research Institute Ghent(CRIG),Ghent University,Ottergemsesteenweg 460,B-9000,Ghent,Belgium [3]Faculty of Biology,Chemistry&Earth Sciences,University of Bayreuth,Universitätsstraße 30,95447 Bayreuth,Germany

出　　处：《Bioactive Materials》2023年第6期524-534,共11页生物活性材料（英文）

摘　　要：Zwitterionic polymers are known to interact with cells and have been shown to reveal cancer cell specificity.In this work,the importance of the chemistry of the polymer backbone for the cellular specificity of amino-acid-derived polyzwitterions is demonstrated.A series of glutamic acid(Glu)-based vinyl monomers(i.e.,an acrylate,a methacrylate,an acrylamide,and a methacrylamide)were prepared and used for reversible addition-fragmentation chain-transfer(RAFT)polymerisation,yielding defined polymers with narrow size distribution(Ð<1.3).All Glu-functionalised,zwitterionic polymers revealed high cytocompatibility;however,differences in cellular association and specificity were observed.In particular,the methacrylamide-derived polymers showed high association with both,breast cancer cells and non-cancerous dendritic cells and,consequently,lack specificity.In contrast,high specificity to only breast cancer cells was observed for polyacrylates,-methacrylates,and-acrylamides.Detailed analysis of the polymers revealed differences in hydrophobicity,zeta potential,and potential side chain hydrolysis,which are impacted by the polymer backbone and might be responsible for the altered the cell association of these polymers.It is shown that a slightly negative net charge is preferred over a neutral charge to retain cell specificity.This was also confirmed by association experiments in the presence of competitive amino acid transporter substrates.The affinity of slightly negatively charged Glu-derived polymers to the xCT Glu/cystine cell membrane antiporter was found to be higher than that of neutrally charged polymers.Our results emphasise the importance of the polymer backbone for the design of cell-specific polymers.This study further highlights the potential to tailor amino-acid-derived zwitterionic materials beyond their side chain functionality.

关 键 词：Amino-acid-functionalised polymer Zwitterionic polymer Cell-specific polymer Cancer-targeting RAFT-Polymerisation 

分 类 号：R318[医药卫生—生物医学工程]