A versatile strategy to construct surface functionalized pH/redox dual stimuli-responsive nanogels for targeted drug delivery

Developing facile, green, and efficient synthetic methodology for preparing surface-functionalized nanogels has attracted tremendous attention in the field of polymer chemistry and biomaterials engineering. Herein, a series of “clickable” P(MAA-PMA) nanogels with reactive alkyne groups were conveniently prepared by “one-pot” reflux-precipitation polymerization (RPP), their particle sizes and zeta potentials are solid content-dependent. Using P(MAA-PMA)-1 nanogels as the model, the physicochemical properties including particle size, surface potential, morphology, solution stability, and pH/redox responsiveness were characterized in detail. Moreover, the pH/redox dual-responsive drug release feature/kinetics and parameters were analyzed using Korsmeyer–Peppas model and Gallagher–Corrigan model. Then the surface of nanogels was facilely modified with various thiol-containing functional ligands via thiol-yne photo click reaction. As targeted drug carriers, doxorubicin (DOX)-loaded folic acid (FA)-functionalized nanogels (FA@Nanogels/DOX) demonstrated higher tumor cell proliferation inhibition effect in B16F10 cancer cells than that in CHO-K1 normal cells, while the non-FA-functionalized counterparts (Nanogels/DOX) do not show similar effect. This work provides a versatile “one-pot RPP-photo Click functionalization” strategy to construct surface-functionalized pH/redox dual responsive nanogels for efficient and targeted drug delivery.