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
|