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 H2O2, 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 H2O2 and the hydrophobic block length. This type of oxidation‐responsive polymer–drug conjugate is feasible for other drugs containing hydroxyl group or amino group.
