Synthesis and Self-Assembly of Well-Defined pH-Responsive Block Glycopolymers

Two pH-responsive block glycopolymers, poly (ethylene glycol)-b-Poly (2- (diethylamino) ethyl methacrylate-co-2-gluconamidoethyl methacrylate) (PEG113-b-P(DEA55-co-GAMA12)) and poly (ethylene glycol)-b-poly (2-(diethylamino) ethyl methacrylate)-b-poly (2-gluconamido ethyl methacrylate) (PEG113-b-PDEA55-b-PGAMA15), were synthesized via atom transfer radical polymerization (ATRP) by directly or successively polymerization of GAMA and DEA monomers using a PEG-based macroinitiator, respectively, without protecting group chemistry. Those block glycopolymers were confirmed by proton Nuclear Magnetic Resonance (1H NMR) and Gel Permeation Chromatography (GPC), and their self-assembly behaviors were characterized by Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS) and Zeta-potential. The results show both synthetic block glycopolymers were dissolved molecularly in aqueous solution at acidic pH (such as pH 3), thus it can reversibly convert to be two-layer micelles comprising DEA and GAMA cores, PEG coronas with size of around 50 nm, or micelles comprising DEA cores, GAMA and PEG outer coronas with bigger size of 70 nm for PEG113-b- P(DEA55-co-GAMA12) and PEG113-b-PDEA55-b-PGAMA15), respectively, at basic condition. Both glycopolymers have the micellization process at middle pH (pH 6-8), but possess different isoelectric points (pIs) (at pH 8.0 and 7.8) for their pH responsive block of PEG113-b-P(DEA55-co-GAMA12) and PEG113-b-PDEA55-b-PGAMA15 with DEA-co-GAMA random structure or DEA chain only, respectively. This study not only reveals the self-assembly of pH responsive block glycopolymers with different architectures by fixing similar degree polymerization (DP) of their blocks, but also provides a tool to investigate pH induced dynamic covalent interaction between glycopolymers and phenylboronic acid derivatives or a light for designing novel drug delivery carriers.