Folic acid-conjugated europium complexes as luminescent probes for selective targeting of cancer cells.

Abstract

We report the synthesis of three optical probes (Eu(3+)⊂1, Eu(3+)⊂2, and Eu(3+)⊂3) having a luminescent Eu complex (signaling unit) bonded in different positions to folic acid (FA), the folate receptor (FR) targeting unit. The structures of the two regioisomers Eu(3+)⊂1 and Eu(3+)⊂2 were assigned by mass spectrometric experiments. The optical properties and stability of these probes were assessed in phosphate-buffered saline, cell culture medium, rat serum, and cellular lysate, and results indicated that they are chemically and photophysically stable. Cytotoxicity was studied with ovarian cancer cells having high (SKOV-3), intermediate (OVCAR-3), low (IGROV-1), or null (A2780) expression of FRs. The internalized probe, evaluated in SKOV-3, IGROV-1, and A2780 cells, was in the order Eu(3+)⊂2 > Eu(3+)⊂1 > Eu(3+)⊂3. No internalization was observed for A2780 cells. Such results, together with those obtained in competition experiments of FA versus Eu(3+)⊂2 and FA or Eu(3+)⊂2 versus (3)H-FA, indicate that internalization is receptor-mediated and that Eu(3+)⊂2 shows high selectivity and specificity for FR.

• Authors: Silvio Quici, Alessandro Casoni, Francesca Foschi, Lidia Armelao, Gregorio Bottaro, Roberta Seraglia, Cristina Bolzati, Nicola Salvarese, Debora Carpanese, Antonio Rosato
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 58 Issue 4 Pg. 2003-14 (Feb 26 2015) ISSN: 1520-4804 [Electronic] United States
• PMID: 25602505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Luminescent Agents
• Molecular Probes
• Organometallic Compounds
• Europium
• Folic Acid

Topics

• Animals
• Cell Line, Tumor
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Stability
• Europium (adverse effects, analysis, chemistry)
• Female
• Folic Acid (adverse effects, chemistry, metabolism)
• Humans
• Luminescent Agents (adverse effects, analysis, chemical synthesis, chemistry)
• Molecular Imaging (methods)
• Molecular Probes (adverse effects, analysis, chemical synthesis, chemistry)
• Molecular Structure
• Organometallic Compounds (adverse effects, analysis, chemical synthesis, chemistry)
• Ovarian Neoplasms (chemistry, metabolism)
• Rats
• Structure-Activity Relationship
• Substrate Specificity