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

Acta Biomater. 2016 Dec:46:151-164. doi: 10.1016/j.actbio.2016.09.027. Epub 2016 Sep 20.

Abstract

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.

Keywords: Bio-imaging; Carbon quantum dots; Drug delivery; Magnetofluorescent; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Carbon / chemistry*
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use*
  • Drug Carriers / chemistry*
  • Drug Delivery Systems*
  • Drug Liberation
  • Fluorescence
  • Folic Acid
  • Gadolinium / chemistry
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Magnetic Phenomena
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Optical Phenomena
  • Particle Size
  • Quantum Dots / chemistry*
  • Spectrophotometry, Ultraviolet
  • Zebrafish

Substances

  • Biocompatible Materials
  • Drug Carriers
  • Carbon
  • Doxorubicin
  • Folic Acid
  • Gadolinium