Intracellular delivery cellulose-based bionanogels with dual temperature/pH-response for cancer therapy

•Synthesis of monodisperse dual stimuli temperature/acidic pH-responsive bionanogels.•Method utilizing aqueous crosslinking via temperature-induced self-association.•Prolonged colloidal stability and negligible non-specific interactions with proteins.•Synergic release of anticancer drugs in response to acidic pH at higher temperature.•Versatility as an effective nanocarrier platform for cancer therapy in vitro. Polysaccharide-based crosslinked nanogles (bionanogels) exhibiting multiple stimuli-responsive release of encapsulated therapeutics hold a great potential as tumor-targeting intracelluar durg delivery nanocarriers. Herein, we report the synthesis of monodisperse dual temperature/acidic pH-responsive bionanogels (DuR-BNGs) by aqueous crosslinking polymerization through temperature-induced self-association method. The DuR-BNGs have prolonged colloidal stability and negligible non-specific interactions with proteins. In response to acidic pH at higher temperature (above lower critical solution temperature), they exhibit synergistic release of anticancer drugs as a consequence of both acidic pH-sensitivity of carboxymethyl cellulose and temperature-induced volume change of grafted thermoresponsive copolymers. In vitro cell culture results suggest that new colloidally-stable DuR-BNG is a promising candidate promoting dual stimuli-responsive drug release for cancer therapy.