title: 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.affiliation: Istituto di Scienze e Tecnologie Molecolari, Consiglio Nazionale delle Ricerche , Via C. Golgi 19, 20133 Milano, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Quici
authors.forename: Alessandro
authors.initials: A
authors.lastname: Casoni
authors.forename: Francesca
authors.initials: F
authors.lastname: Foschi
authors.forename: Lidia
authors.initials: L
authors.lastname: Armelao
authors.forename: Gregorio
authors.initials: G
authors.lastname: Bottaro
authors.forename: Roberta
authors.initials: R
authors.lastname: Seraglia
authors.forename: Cristina
authors.initials: C
authors.lastname: Bolzati
authors.forename: Nicola
authors.initials: N
authors.lastname: Salvarese
authors.forename: Debora
authors.initials: D
authors.lastname: Carpanese
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005063:Europium / Q000009:adverse effects / Q000032:analysis / Q000737:chemistry*; D005260:Female; D005492:Folic Acid / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D049408:Luminescent Agents / Q000009:adverse effects / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry*; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000009:adverse effects / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000009:adverse effects / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D049408:Luminescent Agents; D015335:Molecular Probes; D009942:Organometallic Compounds; D005063:Europium; D005492:Folic Acid