Cyclodextrin Polymers as Delivery Systems for Targeted Anti-Cancer Chemoth

In the few last years, nanosystems have emerged as a potential therapeutic approach toimprove the efficacy and selectivity of many drugs. Cyclodextrins (CyDs) and their nanoparticleshave been widely investigated as drug delivery systems. The covalent functionalization of CyDpolymer nanoparticles with targeting molecules can improve the therapeutic potential of this familyof nanosystems. In this study, we investigated cross-linked - and -cyclodextrin polymers as carriersfor doxorubicin (ox) and oxaliplatin (Oxa). We also functionalized -CyD polymer bearing COOHfunctionalities with arginine-glycine-aspartic or arginine moieties for targeting the integrin receptorsof cancer cells. We tested the Dox and Oxa anti-proliferative activity in the presence of the precursorpolymer with COOH functionalities and its derivatives in A549 (lung, carcinoma) and HepG2 (liver,carcinoma) cell lines. We found that CyD polymers can significantly improve the antiproliferativeactivity of Dox in HepG2 cell lines only, whereas the cytotoxic activity of Oxa resulted as enhanced inboth cell lines. The peptide or amino acid functionalized CyD polymers, loaded with Dox, did notshow any additional effect compared to the precursor polymer. Finally, studies of Dox uptake showedthat the higher antiproliferative activity of complexes correlates with the higher accumulation ofDox inside the cells. The results show that CyD polymers could be used as carriers for repositioningclassical anticancer drugs such as Dox or Oxa to increase their antitumor activity