Tumor cell targeting using folate-conjugated fluorescent quantum dots and receptor-mediated endocytosis

Clin Chem. 2009 May;55(5):955-63. doi: 10.1373/clinchem.2008.113423. Epub 2009 Mar 12.

Abstract

Background: Luminescent nanobioprobes with cell-targeting specificity are likely to find important applications in bioanalysis, biomedicine, and clinical diagnosis. Quantum dots (QDs) are unique and promising materials for such a purpose because of their fluorescence and large surface area for attaching cell-targeting molecules.

Methods: We produced water-dispersible QDs by coating hydrophobic QDs with small amphiphilic polyethylene glycol (PEG) molecules via hydrophobic interactions. We covalently coupled folate (FA) onto the water-dispersible PEG-coated QDs (PEG-QDs) to produce FA-coupled PEG-QDs (FA-PEG-QDs).

Results: These FA-PEG-QD nanoparticles functioned as fluorescent nanobioprobes that specifically recognized folate receptors (FRs) overexpressed in human nasopharyngeal cells (KB cells) but not in an FR-deficient lung carcinoma cell line (A549 cells). Using confocal fluorescence microscopy, we demonstrated uptake of FA-PEG-QDs by KB cells but no uptake of folate-free PEG-QDs. The specificity of this receptor-mediated internalization was confirmed by comparing the uptake by KB vs A549 cells.

Conclusions: Our results suggest that such cell-targeting fluorescent nanobioprobes are potentially very powerful tools for recognizing target cells and delivering and tracking drugs and other therapeutic materials.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Endocytosis
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / pharmacokinetics
  • Folate Receptors, GPI-Anchored
  • Folic Acid / chemistry*
  • Folic Acid / pharmacokinetics
  • Humans
  • KB Cells
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Microscopy, Atomic Force
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacokinetics
  • Quantum Dots*
  • Receptors, Cell Surface / metabolism*
  • Small Cell Lung Carcinoma / drug therapy
  • Small Cell Lung Carcinoma / metabolism*
  • Small Cell Lung Carcinoma / pathology

Substances

  • Carrier Proteins
  • Fluorescent Dyes
  • Folate Receptors, GPI-Anchored
  • Receptors, Cell Surface
  • Polyethylene Glycols
  • Folic Acid