Multifunctional nanocarriers with good biocompatibility, good imaging function, and smart drug delivery ability are crucial for realizing highly efficient imaging-guided chemotherapy in vivo. This paper reports a type of chitosan-carbon dot (CD) hybrid nanogels (CCHNs, ∼65 nm) by integrating pH-sensitive chitosan and fluorescent CDs into a single nanostructure for simultaneous near-infrared (NIR) imaging and NIR/pH dual-responsive drug release to improve therapeutic efficacy. Such CCHNs were synthesized via a nonsolvent-induced colloidal nanoparticle formation of chitosan-CD complexes assisted by ethylenediaminetetraacetic acid (EDTA) molecules in the aqueous phase. The selective cross-linking of chitosan chains in the nanoparticles can immobilize small CDs complexed in the chitosan networks. The resultant CCHNs display high colloidal stability, high loading capacity for doxorubicin (DOX), bright and stable fluorescence from UV to NIR wavelength range, efficient NIR photothermal conversion, and intelligent drug release in response to both NIR light and change in pH. The results from in vitro tests on cell model and in vivo tests on different tissues of animal model indicate that the CCHNs are nontoxic. The DOX-loaded CCHNs can permeate into the implanted tumor on mice and release drug molecules efficiently on site to inhibit tumor growth. The additional photothermal treatments from NIR irradiation can further inhibit the tumor growth, benefited from the effective NIR photothermal conversion of CCHNs. The demonstrated CCHNs manifest a great promise toward multifunctional intelligent nanoplatform for highly efficient imaging-guided cancer therapy with low side effects.

The paper demonstrates a class of multifunctional core-shell hybrid nanogels with fluorescent and magnetic properties, which have been successfully developed for simultaneous optical temperature sensing, tumor cell imaging and magnetic/NIR-thermally responsive drug carriers. The as-synthesized hybrid nanogels were designed by coating bifunctional nanoparticles (BFNPs, fluorescent carbon dots embedded in the porous carbon shell and superparamagnetic iron oxide nanocrystals clustered in the core) with a thermo-responsive poly(N-isopropylacrylamide-co-acrylamide) [poly(NIPAM-AAm)]-based hydrogel as the shell. The BFNPs in hybrid nanogels not only demonstrate excellent photoluminescence (PL) and photostability due to the fluorescent carbon dots embedded in the porous carbon shell, but also has targeted drug accumulation potential and a magnetic-thermal conversion ability due to the superparamagnetic iron oxide nanocrystals clustered in the core. The thermo-responsive poly(NIPAM-AAm)-based gel shell can not only modify the physicochemical environment of the BFNPs core to manipulate the fluorescence intensity for sensing the variation of the environmental temperature, but also regulate the release rate of the loaded anticancer drug (curcumin) by varying the local temperature of environmental media. In addition, the carbon layer of BFNPs can adsorb and convert the NIR light to heat, leading to a promoted drug release under NIR irradiation and improving the therapeutic efficacy of drug-loaded hybrid nanogels. Furthermore, the superparamagnetic iron oxide nanocrystals in the core of BFNPs can trigger localized heating using an alternating magnetic field, leading to a phase change in the polymer gel to trigger the release of loaded drugs. Finally, the multifunctional hybrid nanogels can overcome cellular barriers to enter the intracellular region and light up the mouse melanoma B16F10 cells. The demonstrated hybrid nanogels would be an ideal system for the biomedical applications due to their excellent optical properties, magnetic properties, high drug loading capacity and responsive drug release behavior.