Heteroatom doped carbon dots with nanoenzyme like properties as theranostic platforms for free radical scavenging, imaging, and chemotherapy

• Published in: Acta biomaterialia 2020-09, Vol.114, p.343-357
• Main Authors: Dehvari, Khalilalrahman, Chiu, Sheng-Hui, Lin, Jin-Sheng, Girma, Wubshet Mekonnen, Ling, Yong-Chien, Chang, Jia-Yaw
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Biocompatibility; Cancer; Carbon; Carbon dots; CD44 antigen; Chemotherapy; Conjugation; Controlled release; Doxorubicin; Drug Delivery Systems; Free Radicals; Heteroatom doping; Hyaluronic acid; In vivo methods and tests; Magnetic properties; Magnetic resonance imaging; Medical imaging; Multi-modal probe; Nanoenzyme; Nitrogen; Optical properties; pH effects; Photoluminescence; Photons; Precision Medicine; Quantum Dots; Reactive nitrogen species; Reactive oxygen species; Scavenging; Toxicity; Zebrafish
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2020.07.022

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 dots (MnNS:CDs) nanoenzyme 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. Carbon dots (CDs) have gained increasing interest as emerging and promising artificial functional nanomaterials that mimic the structures and functions of natural enzymes. In this work, Mn, N, and S incorporated CDs (MnNS:CDs) were synthesized using a one-pot microwave hydrothermal method to serve as fluorescent and magnetic resonance imaging probes, and catalase mimics in the reduction of the oxidative-stress related damage. Further conjugation of the probes with hyaluronic acid endows them with a good in vitro and in vivo biocompatibility as well as the capability to selectively target CD44-overexpressing cancer cells, as investigated by in vitro fluorescence, and magnetic resonance imaging. The dual-modal nanoprobe was then used to carry on doxorubicin through a non-covalent association. Favorably, targeted delivery, and pH-responsive release of doxorubicin enhanced cell killing efficiency by 50% as opposed to the free doxorubicin tre