Cyclodextrin Polymers as Delivery Systems for Targeted Anti-Cancer Chemoth
In the few last years, nanosystems have emerged as a potential therapeutic approach to
improve the efficacy and selectivity of many drugs. Cyclodextrins (CyDs) and their nanoparticles
have been widely investigated as drug delivery systems. The covalent functionalization of CyD
polymer nanoparticles with targeting molecules can improve the therapeutic potential of this family
of nanosystems. In this study, we investigated cross-linked
– and -cyclodextrin polymers as carriers
for doxorubicin (ox) and oxaliplatin (Oxa). We also functionalized
-CyD polymer bearing COOH
functionalities with arginine-glycine-aspartic or arginine moieties for targeting the integrin receptors
of cancer cells. We tested the Dox and Oxa anti-proliferative activity in the presence of the precursor
polymer 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 antiproliferative
activity of Dox in HepG2 cell lines only, whereas the cytotoxic activity of Oxa resulted as enhanced in
both cell lines. The peptide or amino acid functionalized CyD polymers, loaded with Dox, did not
show any additional effect compared to the precursor polymer. Finally, studies of Dox uptake showed
that the higher antiproliferative activity of complexes correlates with the higher accumulation of
Dox inside the cells. The results show that CyD polymers could be used as carriers for repositioning
classical anticancer drugs such as Dox or Oxa to increase their antitumor activity
Year |
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2021 |
Journal |
Molecules (Basel, Online) |