New thiol-responsive nanocarriers of amphiphilic block copolymers consisting of a pendent disulfide-labeled methacrylate polymer block (PHMssEt) and a hydrophilic poly(ethylene oxide) (PEO) block were reported. These well-controlled block copolymers were synthesized by atom transfer radical polymerization (ATRP) of a new pendent disulfide-functionalized methacrylate (HMssEt) in the presence of the PEO-Br macroinitiator. Due to its amphiphilic nature, the PEO-b-PHMssEt with narrow molecular weight distribution self-assembled in aqueous solution to form monomodal micellar aggregates with PHMssEt cores surrounded with hydrophilic PEO coronas. In response to thiols, the disulfide linkages were cleaved, and thus self-assembled micelles were either converted to core-crosslinked micelles or destabilized to further disintegrate, depending on the amount of added thiols. Such change in morphology led to tunable release of encapsulated model drugs in aqueous solutions.
