Oxidation-Accelerated Hydrolysis of the Ortho Ester-Containing Acid-Labile Polymers

Abstract

We report a versatile method to tune the hydrolysis of the ortho ester-containing block copolymers by covalently incorporating oxidation-sensitive phenylboronic ester units. A series of block copolymers which contain a polyethylene glycol (PEG) block and a hydrophobic segment composed of different amounts of pendent ortho ester and phenylboronic ester groups were synthesized. These copolymers can self-assemble into narrowly dispersed micelle-like nanoparticles in phosphate buffer. The kinetics of phenylboronic ester oxidation and ortho ester hydrolysis in the nanoparticles were studied at different pH and H 2 O 2 concentration. The results indicated that the phenylboronic ester oxidation rate was faster than the ortho ester hydrolysis rate at neutral pH, and both processes were accelerated with increasing H 2 O 2 concentration. Nanoparticles which are extremely sensitive to the biorelevant concentration of H 2 O 2 (50 μM) at pH 7.4 were obtained, suggesting great promise for inflammationspecific drug delivery.

Curcumin-coordinated nanoparticles with improved stability for reactive oxygen species-responsive drug delivery in lung cancer therapy

“…27 The color change of the nanoparticle with or without H 2 O 2 at different time intervals was photographed for comparison. In addition, both the aqueous solution were centrifuged at 3,000 rpm for 3 min and photographed after 4 h incubation.…”

Reactive Oxygen Species-Activated Nanomaterials as Theranostic Agents

“…Song et al prepared pH and oxidation dual responsive micelle-like materials that were made of ortho ester and phenylboronic ester. Oxidation accelerated hydrolysis of the orthoester at pH 7.4 with H 2 O 2 as pheylboronic ester is oxidized to a catalytic carboxylic acid [87]. Generally, peroxynitrite is formed from a reaction of superoxide radicals with nitric oxide which has deleterious effects on nucleic acid, protein and lipid.…”

Synthesis and Characterization of Homopolymers Bearing Acid‐Cleavable Cationic Side‐Chains for pH‐Modulated Release of DNA

“…There are two possible pathways of hydrolysis for cyclic ortho esters that involve exocyclic and endocyclic breakage of the ortho ester bond . In a recent report, a oxidation sensitive acrylic monomer was copolymerized with a six‐membered ortho ester‐containing pH‐sensitive acrylic monomer to produce a family of block copolymers . This ortho ester hydrolyzed through endocyclic pathways, giving rise to 2,2‐dimethyl‐1,3‐propanediol monoformate and formic acid.…”