Theranostic Polyaminocarboxylate-Cyanine-Transferrin Conjugate for Anticancer Therapy and Near-Infrared Optical Imaging

ChemMedChem. 2016 Oct 6;11(19):2188-2193. doi: 10.1002/cmdc.201600072. Epub 2016 Sep 14.

Abstract

Iron chelation therapy has been recognized as a promising antitumor therapeutic strategy. Herein we report a novel theranostic agent for targeted iron chelation therapy and near-infrared (NIR) optical imaging of cancers. The theranostic agent was prepared by incorporation of a polyaminocarboxylate-based cytotoxic chelating agent (N-NE3TA; 7-[2-[(carboxymethyl)amino]ethyl]-1,4,7-triazacyclononane-1,4-diacetic acid) and a NIR fluorescent cyanine dye (Cy5.5) onto a tumor-targeting transferrin (Tf). The N-NE3TA-Tf conjugate (without Cy5.5) was characterized and evaluated for antiproliferative activity in HeLa, HT29, and PC3 cancer cells, which have elevated expression levels of the transferrin receptor (TfR). The N-NE3TA-Tf conjugate displayed significant inhibitory activity against all three cancer cell lines. The NIR dye Cy5.5 was then incorporated into N-NE3TA-Tf, and the resulting cytotoxic and fluorescent transferrin conjugate N-NE3TA-Tf-Cy5.5 was shown by microscopy to enter TfR-overexpressing cancer cells. This theranostic conjugate has potential application for dual use in targeted iron chelation cancer therapy and NIR fluorescence imaging.

Keywords: anticancer therapy; fluorescent probes; optical imaging; theranostic agents; transferrin conjugates.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carbocyanines / chemistry*
  • Carbocyanines / pharmacology
  • Carboxylic Acids / chemistry*
  • Carboxylic Acids / pharmacology
  • Cell Proliferation / drug effects
  • Chelating Agents / chemical synthesis
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Optical Imaging / methods*
  • Polyamines / chemistry*
  • Polyamines / pharmacology
  • Spectroscopy, Near-Infrared
  • Structure-Activity Relationship
  • Transferrin / chemistry*
  • Transferrin / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • CY5.5 cyanine dye
  • Carbocyanines
  • Carboxylic Acids
  • Chelating Agents
  • Polyamines
  • Transferrin