Heteroatom Doped Carbon Dots with Nanoenzyme Like Properties as Theranostic Platforms for Free Radical Scavenging, Imaging, and Chemotherapy

Carbon-based artificial nanoenzymes have gained increasing interest as emerging and promising nanotheranostic agents due to their biocompatibility, low cost, and straightforward production. Herein, a multifunctional Mn, N, and S incorporated carbon quantum dots (MnNS:CDs) exhibiting scavenging activity against reactive oxygen species (ROS) and reactive nitrogen species (RNS), photoluminescence quantum yield of 17.7 %, and magnetic resonance imaging (MRI) contrast was explored. The optical, magnetic, and antioxidant properties of MnNS:CDs were then regulated by control over Mn incorporation to achieve higher photostability and antioxidant properties. Furthermore, conjugation of MnNS:CDs with hyaluronic acid (HA) (denoted as MnNS:CDs@HA) endowed them with high biocompatibility, which is validated by in vivo studies on zebrafish, and the ability to specifically target cluster determinant 44 (CD44)-overexpressing B16F1 cells, as verified by in vitro confocal and MRI studies. The MnNS:CDs@HA probe with therapeutic antioxidant and dual-modal imaging capability was further assessed for non-covalent binding of doxorubicin (DOX) as a model chemotherapeutic cancer drug. Results showed that targeted delivery and pH-dependent release of DOX elicited apparent cell toxicity (90%) toward B16F1 cancer cells when compared to free DOX treatment group (60%). Benefiting from their intrinsic antioxidant properties, and dual-modal imaging ability, the MnNS:CDs@HA nanocarrier is projected to improve non-invasive targeted diagnosis and therapy.