Doxorubicin conjugated functionalizable carbon dots for nucleus targeted delivery and enhanced therapeutic efficacy

Nanoscale. 2016 Mar 28;8(12):6801-9. doi: 10.1039/c6nr00247a.

Abstract

Carbon dots (CDs) have shown great potential in imaging and drug/gene delivery applications. In this work, CDs functionalized with a nuclear localization signal peptide (NLS-CDs) were employed to transport doxorubicin (DOX) into cancer cells for enhanced antitumor activity. DOX was coupled to NLS-CDs (DOX-CDs) through an acid-labile hydrazone bond, which was cleavable in the weakly acidic intracellular compartments. The cytotoxicity of DOX-CD complexes was evaluated by the MTT assay and the cellular uptake was monitored using flow cytometry and confocal laser scanning microscopy. Cell imaging confirmed that DOX-CDs were mainly located in the nucleus. Furthermore, the complexes could efficiently induce apoptosis in human lung adenocarcinoma A549 cells. The in vivo therapeutic efficacy of DOX-CDs was investigated in an A549 xenograft nude mice model and the complexes exhibited an enhanced ability to inhibit tumor growth compared with free DOX. Thus, the DOX-CD conjugates may be exploited as promising drug delivery vehicles in cancer therapy.

MeSH terms

  • A549 Cells
  • Active Transport, Cell Nucleus
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Apoptosis
  • Calibration
  • Carbon / chemistry*
  • Cell Nucleus / drug effects*
  • Cell Nucleus / metabolism
  • Doxorubicin / administration & dosage*
  • Drug Delivery Systems
  • Electron Spin Resonance Spectroscopy
  • Flow Cytometry
  • Gene Transfer Techniques
  • Humans
  • Hydrazones / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microscopy, Atomic Force
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Necrosis
  • Neoplasm Transplantation
  • Neoplasms / drug therapy
  • Optics and Photonics
  • Protein Sorting Signals
  • Quantum Dots*
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Antibiotics, Antineoplastic
  • Hydrazones
  • Protein Sorting Signals
  • Carbon
  • Doxorubicin