Folate–Cyclodextrin Conjugates as Carriers of the Platinum(IV) Complex LA-12

July 28, 2017


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






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.




Circular dichroism, Pharmaceutical