Study On The Synthesis And Properties Of Environmentally Sensitive Glycopolymers

Synthetic glycopolymers and glycoconjugates are not only used to study their rolesin biological processes but also applied to various important biomedical applications. Thedevelopment of novel environmentally sensitive glycopolymers have major impact on thefield of glyco-biomaterials. Hererin, we present the synthesis of various pH andthermo-responsive glycopolymers. These glycopolymers exhibited environmentalresponsibility, specific recongization with lectin, biodegradability and goodbiocompatibility. Further, based on these glycopolymers, shell cross-linkedglyco-nanoparticles have been prepared. The shell cross-linked glyco-nanoparticles hadpH responsibility, specific recongization with lectin and good biocompatibility.The main content are as follows：1) A new class of biodegradable, biomimetic and thermo-responsive dextran/syntheticglycopolymer biohybrids (dextran-graft-poly(lactobionamidoethyl methacrylate)-block-poly(di(ethyleneglycol) methyl ether methacrylate), Dextran-g-(PLAMA-b-PDEGMA)), was synthesized by the directatom transfer radical polymerization (ATRP) of unprotected lactobionamidoethyl methacrylate (LAMA)glycomonomer and di(ethylene glycol) methyl ether methacrylate (DEGMA) monomer. The dextranmacroinitiator for ATRP was prepared by partial esterification of the hydroxyl groups of thepolysaccharide with2-bromo-2-methylpropionic acid (BrMPA). The biohybrids containing PDEGMAsegments exhibited the thermosensitive properties with a LCST around36℃, whichchanged from unimers to aggregates in solutions. Moreover, it was demonstrated thatthese biohybrids had specific biomolecular recognition with ricinus communis agglutinin120(RCA120) in comparison with bovine serum albumin (BSA). Furthermore, thesebiohybrids showed good biocompatibility in the cytotoxicity assays. This hopefullyprovides a platform for targeted drug delivery and studying the biomolecular recognitionbetween sugar and lectin.2) New pH-responsive glycopolymer PGAMA-b-P(DMAEMA-co-DEAEMA) has been designed and successfully synthesized by “one-pot” polymerization. Thisglycopolymer was prepared via atom transfer radical polymerization in a convenientone-pot synthesis and comprised a pH-sensitive core-forming PDEAEMA block and asaccharide-functional outer block based on PGAMA. The architectures of theglycopolymers were confirmed by FT-IR,1H-NMR and GPC. DLS and DSA tests werealso performed to investigate the solution properties of the glycopolymer. This newglycopolymer contained a polyelectrolyte block and exhibited tunable pH-responsibilityin water. It was also demonstrated that the biohybrids had specific biomolecularrecognition with ricinus communis agglutinin120(RCA120) in comparison with bovineserum albumin (BSA) at alkaline pH. While the environmental pH was below7, theglycopolymer was partially charged and had nonspecific interaction with proteinpossessing opposite charges. Further, the fluorescence spectrum showed that theglycopolymer basically didn’t change the stability of proteins. The CCK-8assaysrevealed the glycopolymer had good biocompatibility.3) Shell cross-linked (SCL) micelles with saccharide-functional coronas have beenconstructed in aqueous solution by exploiting the micellar self-assembly behavior of anew pH-sensitive ABC triblock glycopolymer. This glycopolymer was prepared via atomtransfer radical polymerization and comprised a pH-sensitive core-forming PDEAEMAblock, a cross-linkeable central PDMAEMA block, and a saccharide-functional outerblock based on PGAMA. The architectures of the glycopolymers were confirmed byFT-IR,1H-NMR and GPC. This triblock glycopolymer molecularly dissolved in acidicmedia and self-assembled at alkaline pH. Selective cross-linking of the PDMAEMA innershell with2-bis(2-iodoethoxy) ethane led to structurally stabilized SCL micellesfunctionalized with surface saccharide groups. The obtained SCL micelles exhibitedpH-sensitive swelling/deswelling behavior, as revealed by DLS. The SCL micelles hadspecific interaction with lectin ConA. Further, the AuNPs formed from autoreduction oftetrachloroauric acid within SCL micelles. These SCL micelles containing AuNPsexihibited interesting pH-sensitive property, lectin recongnition and goodbiocompatibility. 4) Novel glycopolymers containing polyelectrolyte were successfully synthesized byatom transfer radical polymerization. The architectures of the glycopolymers wereconfirmed by1H-NMR and GPC. DLS and Zeta-potential tests were also performed toinvestigate the solution properties of the glycopolymers. We found that the novelglycopolymers exhibited multi-temperature responsive property.