Aqueous self-assembled nanostructures driven from polysaccharide-based copolymers exhibiting enhanced colloidal stability and rapid release ability are promising candidates as polymer-based drug delivery nanocarriers. Herein, we report the synthesis, thermoresponsiveness, aqueous micellization, and in situ-disulfide crosslinking of hydroxypropyl cellulose (HPC)-based grafted copolymers exhibiting dual reduction-responsive and thermoresponsive properties. They are synthesized by grafting from method utilizing atom transfer radical polymerization of a mixture of two methacrylate monomers containing pendant disulfide linkage (HMssEt) and oligo(ethylene oxide) (OEOMA). Their thermal properties are tuned with pendant hydrophobic/hydrophilic balance. Aqueous micellization through self-assembly, followed by in situ disulfide-crosslinking through thiol-disulfide exchange reaction allows for the formation of disulfide-crosslinked nanogels with excellent colloidal stability upon dilution. The formed nanogels exhibit reduction-responsive degradation in the presence of excess cellular reducing agent such as glutathione. We envision that HPC-based disulfide-crosslinked nanogels can offer versatility in tumor-targeting drug delivery for enhanced colloidal stability and rapid drug release. (C) 2015 Elsevier Ltd. All rights reserved.