Cationic conjugated polymer/fluoresceinamine-hyaluronan complex for sensitive fluorescence detection of CD44 and tumor-targeted cell imaging

ACS Appl Mater Interfaces. 2014;6(21):19144-53. doi: 10.1021/am505113p. Epub 2014 Oct 14.

Abstract

Simple, rapid, and sensitive detection of CD44 is of paramount importance since it plays pivotal roles in tumor initiation, growth and metastasis. Herein, we describe a novel method for sensitive, visual and facile fluorescence detection of CD44 and CD44-mediated cancer cell imaging, using a probe based on cationic conjugated polymer (CCP)-PFEP and fluoresceinamine-hyaluronan (FA-HA). HA is an anionic natural glycosaminoglycan that can specifically bind to the overexpressed CD44 on various kinds of cancer cells. PFEP and FA-HA formed a complex through electronic interactions, resulting in a highly efficient fluorescence resonance energy transfer (FRET) from PFEP to FA-HA; moreover, the efficiencies of FRET correlated with the concentrations of CD44 because the specific binding of HA-CD44 would separate FA-HA away from PFEP. This method did not require laborious and expensive dual-labeling or protein-labeling needed in previously reported detection methods of CD44. Just mix the sample and test solution containing the PFEP/FA-HA complex, and the results allowed naked-eye detection by observing fluorescent color of solutions with the assistance of a UV lamp. Most importantly, the use of a conjugated polymer with excellent amplification property as well as the specific binding of HA-CD44 endowed this method with high sensitivity and specificity, making it applicable for reliable quantitative detection of CD44. Furthermore, the PFEP/FA-HA complex formed nanoparticles in aqueous solution, and the nanoparticles can be selectively taken up by MCF-7 cells (cancer cell) through the HA-CD44 interaction, thereby giving rise to a dual-color tumor-targeted imaging probe with good photostability. The development of this fluorescent probe showed promising potential to make a reliable and routine method available for early diagnosis of cancer.

Keywords: CD44; cationic conjugated polymer; cell imaging; fluoresceinamine-hyaluronan; fluorescence resonance energy transfer (FRET).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cations / chemistry
  • Cell Line, Tumor
  • Drug Delivery Systems / methods*
  • Fluoresceins / chemistry*
  • Fluorescence Resonance Energy Transfer
  • Fluorescent Dyes / chemistry
  • Humans
  • Hyaluronan Receptors / analysis*
  • Hyaluronic Acid / chemistry*
  • Hyaluronic Acid / pharmacokinetics
  • Nanoparticles / chemistry*
  • Neoplasms / metabolism*
  • Nuclear Magnetic Resonance, Biomolecular
  • Polymers / chemistry
  • Polymers / pharmacokinetics

Substances

  • Cations
  • Fluoresceins
  • Fluorescent Dyes
  • Hyaluronan Receptors
  • Polymers
  • Hyaluronic Acid