Dual-stimuli reduction and acidic pH-responsive bionanogels: intracellular delivery nanocarriers with enhanced release

Biopolymer-based nanogels (bionanogels) are a promising platform as polymer-based drug delivery systems encapsulting hydrophilic anticancer therapeutics; however, enhanced/controlled drug release is highly desired. Herein, we report new dual stimuli-responsive bionanogels (ssBNGs) as potential intracellular delivery nanocarriers with multi-controlled and enhanced drug release. A facile aqueous crosslinking polymerization of oligo(ethylene oxide)-containing methacrylate (OEOMA) in the presence of carboxymethyl cellulose (CMC) and a disulfide-labeled dimethacrylate allows for the synthesis of ssBNGs crosslinked with disulfide linkages of POEOMA-grafted CMC. These ssBNGs exhibit dual response release of encapsulated anticancer drugs: reductive cleavage of disulfide crosslinks and acidic pH-response of carboxylic acid groups in CMC. Their applicability toward tumor-targeting drug delivery applications is demonstrated with confocal laser scanning microscopy for cellular uptake and cell viability, as well as a facile bioconjugation with a water-soluble UV-active dye as a model cell-targeting biomolecule.