Biocompatible PEG-Chitosan@Carbon Dots Hybrid Nanogels for Two-Photon Fluorescence Imaging, Near-Infrared Light/pH Dual-Responsive Drug Carrier, and Synergistic Therapy

This work designs a class of biocompatible PEG-chitosan@CDs hybrid nanogels by integrating nonlinear poly(ethylene glycol) (PEG), chitosan, and graphitic carbon dots (CDs) into a single nanoparticle for two-photon fluorescence (TPF) bioimaging, pH and near-infrared (NIR) light dual-responsive drug release, and synergistic therapy. Such hybrid nanogels can be simply prepared from a one-pot surfactant-free precipitation polymerization of the PEG macromonomers complexed with chitosan and CDs in water, resulting in a semi-interpenetration of chitosan chains and an immobilization of CDs in the nonlinear PEG networks. The embedded CDs in hybrid nanogels not only serve as an excellent confocal and TPF imaging contrast agent and fluorescent pH-sensing probe, but also enhance the loading capacity of the hybrid nanogels for hydrophobic anticancer drug. The chitosan can induce a pH-sensitive swelling/deswelling of the hybrid nanogels for pH-regulated drug release over the physiologically important range of 5.0-7.4 and surface modulation of embedded CDs to realize fluorescent pH sensing. The thermosensitive nonlinear PEG network can promote the drug release through the local heat produced by the embedded CDs under NIR irradiation. The in vitro results indicate that the hybrid nanogels demonstrated high therapeutic efficacy through the synergistic effect of combined chemo-photothermal treatments.