Temperature and Redox Dual-Responsive Biodegradable Nanogels for Optimizing Antitumor Drug Delivery.

The strategy to efficiently deliver antitumor drugs via nanocarriers to targeted tumor sites and achieve controllable drug release is attracting great research interest in cancer therapy. In this study, a novel type of disulfide-bonded poly(vinylcaprolactam) (PVCL)-based nanogels with tunable volume phase transition temperature and excellent redox-labile property are prepared. The nanogels are hydrophilic and swell at 37 °C, whereas under hyperthermia (e.g., 41 °C), the nanogels undergo sharp hydrophilic/hydrophobic transition and volume collapse, which enhances the cellular uptake and drug release. The incorporation of disulfide bond linkers endows the nanogels with an excellent disassembly property in reducing environments, which greatly facilitates drug release in tumor cells. Nanogels loaded with doxorubicin (DOX) (DOX-NGs) (DOX-NGs) are stable in physiological conditions with low drug leakage (15% in 48 h), while burst release of DOX (92% in 12 h) can be achieved in the presence of 10 × 10−3 m glutathione and under hyperthermia. The DOX-NGs possess improved cell killing efficiency under hyperthermia (IC50 decreased from 1.58 μg mL−1 under normothermia to 0.5 μg mL−1). Further, the DOX-NGs show a pronounced tumor inhibition rate of 46.6% compared with free DOX, demonstrating that this new dual-responsive nanogels have great potential as drug delivery carriers for cancer therapy in vivo. [ABSTRACT FROM AUTHOR]