We report a new type of oxidation-promoted fast-degradable aliphatic poly­(carbonate)­s (PCs) prepared by the ring-opening polymerization (ROP) of a six-membered cyclic carbonate containing a phenylboronic pinacol ester. The ROP of this monomer catalyzed by 1,8-diazabicyclo[5.4.0]­undec-7-ene (DBU) proceeded rapidly at ambient temperature with a good control over molecular weight and polydispersity at high monomer conversion. The H2O2-induced decomposition of this cyclic monomer and its noncyclic carbonate analogue was first studied by 1H NMR in order to clearly demonstrate the degradation mechanism of the PCs. The results of 1H NMR, GPC, and Nile Red fluorescence measurements revealed that the PC nanoparticles formulated by the o/w emulsion method were stable in neutral buffer, but upon triggering with H2O2, they underwent rapid surface degradation via the consecutive processes of oxidation, 1,6-elimination, release of CO2, and intramolecular cyclization. The degradation rates of the nanoparticles were dependent on the concentration of H2O2, and the nanoparticles were even sensitive to 0.5 mM of H2O2.

Functional polyesters and poly(carbonate)s (PCs) with controlled and on-demand degradation properties have great advantages for biomedical and pharmaceutical applications. Herein, we report a new kind of aliphatic PC that possesses the feature of oxidation promoted degradation. Two six-membered cyclic carbonates (C1 and C2) containing phenylboronic ester group have been synthesized from serinol (1) and 2-aminomethyl-2-methylpropane-1,3-diol (2), respectively. Both monomers could undergo wellcontrolled ring-opening polymerization (ROP) catalyzed by an organic base, but the 5,5-disubstituted C2 has the character of equilibrium ROP and a much slower rate than the monosubstituted C1. The copolymerization of C1 or C2 with trimethylene carbonate and its derivative leads to a series of copolymers. Two series of amphiphilic block copolymers (BPC1s and BPC2s) have been prepared from C1 and C2 using poly(ethylene glycol) as the macroinitiator. They are able to form nanoparticles with the diameters less than 150 nm. The H 2 O 2 -triggered decomposition of C1, C2, and their corresponding noncyclic model compounds was studied by 1 H NMR, showing the consecutive process of oxidation, 1,6elimination, release of CO 2 , and intramolecular isomerization or cyclization. The degradation of the block copolymer nanoparticles, investigated by 1 H NMR, GPC, laser light scattering (LLS), and Nile Red fluorescence, can also be accelerated drastically by H 2 O 2 following the similar mechanism but is affected by steric hindrance of the polymer chain and heterogeneous microenvironment inside the nanoparticles. The results of 1 H NMR and LLS reveal that the nanoparticles of BPC1 and BPC2 exhibited different degradation profiles, with a slightly faster degradation rate for BPC2. Of particular interest, BPC2 nanoparticle is sensitive to as low as 0.02 mM H 2 O 2 .

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.