Nitric oxide (NO) cleavable biomimetic thermoresponsive double hydrophilic diblock copolymer with tunable LCST

The fabrication of responsive biomimetic polymers that can respond to externally applied stimuli has received considerable attention over the past few years due to the variety of potential applications. Herein, we report a convenient method to fabricate a thermoresponsive diblock copolymer that is sensitive to a biological messenger molecule, nitric oxide (NO). A well-defined thermoresponsive double hydrophilic block copolymer (DHBC) of poly(ethylene glycol)-b-poly(N-isopropylacrylamide) (PEG-b-PNIPAM) was initially synthesized via atom radical transfer polymerization (ATRP) using a PEG-Cl macroinitiator including an o-nitroaniline motif. The o-nitroaniline derivative was subjected to reduction in the presence of a reducing agent (zinc powder), yielding DHBC with a single amide-functionalized o-phenylenediamine moiety (an efficient NO-reactive group) at the chain junction point. Upon addition of a near equivalent amount of NO (relative to the o-phenylenediamine residues), the o-phenylenediamine groups were transformed to benzotriazoles, resulting in spontaneous hydrolysis (as confirmed by UV-vis and GPC measurements). This resulted in scission of the original diblock copolymers and therefore a substantial decrease in the lower critical solution temperature (LCST) (due to the loss of the hydrophilic PEG chains). NO-triggered cleavage of the hydrophilic block of a DHBC may have potential application in NO-mediated drug release.