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 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.

Rapid fabrication of carbon quantum dots as multifunctional nanovehicles for dual-modal targeted imaging and chemotherapy.

Herein, we synthesized an S, N, and Gd tri-element doped magnetofluorescent carbon quantum dots (GdNS@CQDs) within 10min by using a one-pot microwave method. Our results showed that these magnetofluorescent GdNS@CQDs have excellent fluorescent and magnetic properties. Moreover, GdNS@CQDs exhibited high stability at physiological conditions and ionic strength. These magnetofluorescent GdNS@CQDs were conjugated with a folic acid, denoted as FA-GdNS@CQDs, for targeting dual modal fluorescence/magnetic resonance (MR) imaging. The in vitro and in vivo studies confirmed the high biocompatibility and low toxicity of FA-GdNS@CQDs. FA-GdNS@CQDs enhanced the MR response as compared to that for commercial Gd-DTPA. The targeting capabilities of FA-GdNS@CQDs were confirmed in HeLa and HepG2 cells using in vitro fluorescence and MR dual modality imaging. Additionally, an anticancer drug, doxorubicin, was incorporated into the FA-GdNS@CQDs forming FA-GdNS@CQDs-DOX, which enables targeted drug delivery. Importantly, the prepared FA-GdNS@CQDs-DOX showed a high quantity of doxorubicin loading capacity (about 80%) and pH-sensitive drug release. The uptake into cancer cells and the intracellular location of the FA-GdNS@CQDs were observed by confocal laser scanning microscopy. We also successfully demonstrated in vivo fluorescence bio imaging of the FA-GdNS@CQDs, using zebrafish as an animal model. STATEMENT OF SIGNIFICANCE: In this manuscript, we reported a facial, rapid, and environmental friendly method to fabricate hetero atoms including gadolinium, nitrogen, and sulfur doped multi-functional magnetofluorescent carbon quantum dots (GdNS@CQDs) nanocomposite. These multifunctional GdNS@CQDs were conjugated with a folic acid for targeting dual modal fluorescence/magnetic resonance imaging. Additionally, an anticancer drug, doxorubicin, was incorporated into the nanocomposite forming FA-GdNS@CQDs-DOX, which enables targeted drug delivery. We have developed GdNS@CQDs with integrated functions for simultaneous in vitro cell imaging, targeting, and pH-sensitive controlled drug release in HeLa cells. Furthermore, we successfully demonstrated the use of this material for in vivo fluorescence imaging, using zebrafish as an animal model.