Cyclodextrin polymers as carriers for the platinum-based anticancer agent LA-12

Polymeric nanoparticles containing cyclodextrins are currently undergoing clinical trials as nanotherapeutics. In this context, we have synthesized high and low molecular weight beta-cyclodextrin polymers and functionalized them with folate to improve their selectivity for cells overexpressing the folic acid receptor. Inclusion complexes of the unfunctionalized and FA-functionalized polymers with the antitumour complex cis-trans-cis-[PtCl2(CH3CO2)(2)(adamantyl-NH2)(NH3)] (LA-12) have been tested on tumour cells. In the presence of the high molecular weight polymers, LA-12 exhibited IC50 values significantly lower than that of LA-12 alone in MDA-MB-231 cells. The drug nanocarriers investigated do not appear to take significant advantage of the presence of folate residues, possibly because of the reduced accessibility of folate included in cyclodextrin moieties by the receptor or low degree of functionalization of the polymers. However the non-covalent approach, based on inclusion complexes with cyclodextrin polymers, looks very promising for improving the performance of LA-12.