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

• Published in: Acta biomaterialia 2016-12, Vol.46, p.151-164
• Main Authors: Chiu, Sheng-Hui, Gedda, Gangaraju, Girma, Wubshet Mekonnen, Chen, Jem-Kun, Ling, Yong-Chien, Ghule, Anil V., Ou, Keng-Liang, Chang, Jia-Yaw
• Format: Article
• Language: English
• Subjects: Animals; Bearing strength; Bio-imaging; Biocompatibility; Biocompatible Materials - chemistry; Cancer; Carbon; Carbon - chemistry; Carbon quantum dots; Chemotherapy; Confocal microscopy; Danio rerio; Doxorubicin; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Drug Carriers - chemistry; Drug delivery; Drug Delivery Systems; Drug Liberation; Fabrication; Fluorescence; Folic Acid; Gadolinium - chemistry; HeLa Cells; Hep G2 Cells; Humans; Imaging; In vitro methods and tests; In vitro testing; In vivo methods and tests; Ionic strength; Magnetic Phenomena; Magnetic properties; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Magnetofluorescent; Mice; Microscopy; Nanocomposites; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Optical Phenomena; Particle Size; pH effects; Quantum dots; Quantum Dots - chemistry; Qunatum dots; Scanning microscopy; Spectrophotometry, Ultraviolet; Toxicity; Zebrafish
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2016.09.027

[Display omitted] 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. 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.