Heteroatom doped carbon dots with nanoenzyme like properties as theranostic platforms for free radical scavenging, imaging, and chemotherapy. (15th September 2020)

• Record Type: Journal Article
• Authors: Dehvari, Khalilalrahman; Chiu, Sheng-Hui; Lin, Jin-Sheng; Girma, Wubshet Mekonnen; Ling, Yong-Chien; Chang, Jia-Yaw
• Is Part Of: Acta biomaterialia. Volume 114(2020)
• Page Start: 343
• Page End: 357
• Publication Date: 2020-09-15
• Subjects: Heteroatom doping -- Carbon dots -- Nanoenzyme -- Multi-modal probe -- Magnetic resonance imaging -- Controlled release; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2020.07.022
• Languages: English
• ISSNs: 1742-7061

Abstract

Abstract: 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. Statement of significance: 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 treatment group. The presented theranostic heteroatom doped CDs hold great promise for dual-modal imaging enabling accurate diagnosis coupled with therapeutic effect through free radical scavenging and chemotherapy. Graphical abstract: Image, graphical abstract