Folate–Cyclodextrin Conjugates as Carriers of the Platinum(IV) Complex LA‐12. Issue 3 (11th November 2014)

• Record Type: Journal Article
• Authors: Giglio, Valentina; Oliveri, Valentina; Viale, Maurizio; Gangemi, Rosaria; Natile, Giovanni; Intini, Francesco P.; Vecchio, Graziella
• Is Part Of: ChemPlusChem. Volume 80:Issue 3(2015:Mar.)
• Page Start: 536
• Page End: 543
• Publication Date: 2014-11-11
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1002/cplu.201402342
• Languages: English
• ISSNs: 2192-6506

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 <italic>cis</italic>–<italic>trans</italic>–<italic>cis</italic>‐[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.</p> </abstract>