In
cancer treatment, developing ideal anticancer drug delivery systems to target tumor microenvironment by circumventing various physiological barriers still remains a daunting challenge. Here, in our work, a series of pH- and temperature-responsive
nanogels based on
poly(N-isopropylacrylamide-co-1-
propene-2-3-dicarboxylate-co-2-acrylamido-2-methyl-1-
propanesulfonate [poly(NIPAAm-IA-AMPS)] cross-linked by
ethylene glycol dimethacrylate (EGDMA) were synthesized by random copolymerization. The molar ratio between monomer-comonomers-cross-linker was varied to fine-tune the optimum responsiveness of the
nanogels. These optimized
nanogels were further coupled to
N,O-carboxymethyl chitosan (
NOCC) stoichiometrically using
EDC-NHS coupling chemistry to enhance the swelling behavior at lower pH. Interestingly, these
NOCC-g-
nanogels, when dispersed in aqueous media under sonication, attain nanosize and retain their high water-retention capacity with conspicuous pH and temperature responsiveness (viz.
nanogel shrinkage in size beyond 35 °C and swelled at acidic pH) in vitro, as reflected by dynamic light scattering data.
Doxorubicin (DOX), a potent anticancer
drug, was loaded into these
nanogels using the physical entrapment method. These
drug-loaded
nanogels exhibited a slow and sustained DOX release profile at physiological temperature and cytosolic pH. Furthermore, confocal and TEM results demonstrate that these
nanogels were swiftly internalized by MCF-7 cells, and cell viability data showed preferential heightened cytotoxicity toward
cancer cells (MCF-7 and MDA-MB231) compared to the MCF10A cells (human breast epithelial cell). Furthermore, intracellular DNA damage and cell cycle arrest assays suggest a mitochondrial mediated apoptosis in MCF-7 cells. This study substantiates our
NOCC-g-
nanogel platform as an excellent modality for passive diffusive loading and targeted release of entrapped
drug(s) at physiological conditions in a controlled way for the improved therapeutic efficacy of the
drug in anticancer treatment.