The Synthesis And Application Of Hydroxyl-Rich Poly(Thioether Ester)s And Its Mielles

Nowadays, cancer has become one of the leading causes of death worldwide. As one of the three mainstream cancer therapeutic methods, chemotherapy usually suffers from quick metabolism of the drug during blood circulation and lack of tumor targeting, which subsequently leads to low therapeutic effect and high side toxicity. Thus, polymeric nano-drug delivey system has been developed with enhanced therapeutic effecicy and reduced side toxicity, which was promoted as promising route to innovative chemotherapy. Polyesters have beome one of the most studied materials for constructure of drug delivery vechicle owing to their excellent biodegradblity and good biocompatibility. However, the simplex physicochemical properoty and chain structure also set limit to the wide application of the traditional polyester materials.To address this issue, we herein developed a facile synthesis route to hydroxyl-rich polyester by simultaneous thiol-ene and thiol-epoxy click condensation polymerization of commercial available 1,2-ethanedithiol(EDT)(or dithiothreitol, DTT) with glycidyl methacrylate(GMA). Based on this method, it not only can avoid the tedious protection-deprotection processes during the synthesis of functionalized polyester, but also can obtain the tunable hydroxyl functionalzed polyesters by simply adjusting the EDT and DTT feed ratio. The resultant poly(thiolether ester)s were then characterized by ~1H NMR, ~13 C NMR and FT IR. Water contact angle measurements further indicated that the hydrophylicity of the poly(thiolether ester) would improved with increasing hydroxyl groups in the side chains. Meanwhile, the cell adhension and proliferation tests revealed that the polyester bearing a set number of hydroxyl groups had preferable cell adhension and proliferation ability, while overabound hydroxyl groups would make the polyester more hydrophilic and subsequently result in lower cell adhension and proliferation. Additionally, the poly(thiolether ester)s were expected to be oxidation sensitive due to the precence of thiolether group in the main chain. The nanoparticles of the polyesters were firstly prepared by nanoprecipitation and moniotered by tubidity assay and DLS measurements. Both of the results indicated the oxidation rate of the polyesters would increase with the improved hydrophilicity of the poly(thiolether ester)s or the increase amount of hydrogen peroxide added. Furthermore, the synthesized poly(thiolether ester)s were also demostraterd to be of geat potential for biofunctionality by the successful conjugation of cholesterol and camptothecin onto the side chain.In order to broaden the biomedical applications of the hydroxyl-rich poly(thiolether ester)s, a block and a grafting copolymers of poly(thiolether ester) and poly(ethylene glycol) methyl ether(m PEG) were synthesized. The block copolymer PGE-b-m PEG5000 could self-assembly into micelles in the aqeous media and relased the encapsulated rodamine B in a oxidation sensitive manner. The grafting copolymers PGE-g-m PEG2000 was further modified with lipoic acid and the resultant copolymers were then transferred into core-corss linked micelles in basic aqueous media due to the base-induced thiol-disulfide exchages. The model drug, doxorubicin(DOX), can be efficiently encapsultated into the core-corss linked micelles and released in response to the glutathione(GSH). In general, all the results indicated that the synthesized poly(thiolether ester)s woiuld be promising for biomedical applications, expecially in constucture of drug delivery systems and tissue engineering scanfold.