Biocompatible Chitosan-Carbon Dot Hybrid Nanogels for NIR-Imaging-Guided Synergistic Photothermal-Chemo Therapy

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.