Folate-cyclodextrin conjugates as carriers of the platinum(IV) complex LA-12

Valentina Giglio, Valentina Oliveri, Maurizio Viale, Rosaria Gangemi, Giovanni Natile, Francesco P. Intini, Graziella Vecchio

Research output: Contribution to journalArticlepeer-review


Folic acid has emerged as an interesting cell-targeting moiety and a number of drugs have been conjugated to folate. In this context, new conjugates of β-cyclodextrins with folate have been synthesised as drug carriers to improve their selectivity for cells overexpressing the folic acid receptor. In particular, both 3- and 6-functionalised β-cyclodextrins, linked to the α- or γ-carboxylic group of folic acid, have been synthesised and fully characterised. As a proof of concept, the antitumour platinum(IV) complex cis-trans-cis-[PtCl2(CH3CO2)2(adamantylamine)(NH3)] (LA-12) has been used as a guest drug. The LA-12-cyclodextrin inclusion complexes have been tested on tumour cells. In the presence of cyclodextrin-folate conjugates, LA-12 exhibited IC50 values four times smaller than those of LA-12 alone in MDA-MB-231 cells, which overexpress folic acid receptors on their membrane. No improvement of LA-12 cytotoxicity was found in control tumour cells that do not overexpress the folate receptor. Thus, the non-covalent approach, based on inclusion complexes with functionalised cyclodextrins, looks very promising for drug targeting. Drugs included: The antitumor drug cis-trans-cis-[PtCl2(CH3CO2)2(adamantlyamine)(NH3)] (LA-12) co-administered with 3- or 6-functionalised β-cyclodextrin conjugated with γ-folate (βCyD3-FAγ or βCyD6-FAγ) as an inclusion complex showed IC50 values significantly lower than that of LA-12 alone or LA-12 co-administered with βCyD in folate receptor-overexpressing cancer cells (see figure).

Original languageEnglish
Pages (from-to)536-543
Number of pages8
Issue number3
Publication statusPublished - 2015


  • antitumor agents
  • conjugation
  • cyclodextrins
  • drug delivery
  • platinum

ASJC Scopus subject areas

  • Chemistry(all)


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