title: Oxidation-Responsive Polymer-Drug Conjugates with a Phenylboronic Ester Linker.
abstract: Polymer-drug conjugates have attracted great interest as one category of various promising nanomedicines due to the advantages of high drug-loading capacity, negligible burst release, and improved pharmacokinetics as compared with the small molecular weight drugs or the polymeric delivery systems with physically encapsulated drugs. Herein, a new type of oxidation-responsive polymer-drug conjugates composed of a poly(ethylene glycol) (PEG) block and a hydrophobic polyacrylate block to which Naproxen is attached through a phenylboronic ester linker is reported. The amphiphilic block copolymers are synthesized through the reversible addition-fragmentation chain transfer polymerization of the Naproxen-containing acrylic monomer using a PEG chain transfer agent. In neutral aqueous buffer, the conjugates formed nanoparticles with diameters of ≈150-300 nm depending on the length of the hydrophobic segment. The dynamic covalent bond of the phenylboronic ester is stabilized due to the hydrophobic microenvironment inside the nanoparticles. Upon exposure to H2 O2 , the phenylboronic ester is oxidized rapidly into the phenol derivative which underwent a 1,6-elimination reaction, releasing the intact Naproxen. The rate of drug release is influenced by the concentration of H2 O2 and the hydrophobic block length. This type of oxidation-responsive polymer-drug conjugate is feasible for other drugs containing hydroxyl group or amino group.
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, Center for Soft Matter Science and Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, P. R. China.
authors: Fang-Yi
authors: FY
authors: Qiu
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, Center for Soft Matter Science and Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, P. R. China.
authors: Mei
authors: M
authors: Zhang
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, Center for Soft Matter Science and Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, P. R. China.
authors: Ran
authors: R
authors: Ji
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, Center for Soft Matter Science and Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, P. R. China.
authors: Fu-Sheng
authors: FS
authors: Du
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, Center for Soft Matter Science and Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, P. R. China.
authors: Zi-Chen
authors: ZC
authors: Li
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D001897:Boronic Acids / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D004952:Esters; D006861:Hydrogen Peroxide / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008823:Micelles; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009288:Naproxen / Q000737:chemistry*; D010084:Oxidation-Reduction; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D058105:Polymerization
chemical_list: D000180:Acrylic Resins; D001897:Boronic Acids; D004337:Drug Carriers; D004952:Esters; D008823:Micelles; D011092:Polyethylene Glycols; C006903:carbopol 940; D009288:Naproxen; D006861:Hydrogen Peroxide; C010686:benzeneboronic acid
keywords: RAFT; naproxen; oxidation-responsive; phenylboronic ester; polymer-drug conjugates