A smart β-Cyclodextrin-Aza[5]Helicene system for enhanced gemcitabine delivery and tracking in cancer cells

A novel beta-cyclodextrin-aza[5]helicene conjugate as theranostic platform for anticancer agents delivery in cancer cells is here reported. The carrier was synthesized via monotosylation of hydroxyethyl-beta-cyclodextrin (HE-beta-CD), followed by reaction with the synthesized aza[5]helicene, yielding the corresponding ammonium tosylate salt. The system was characterized by NMR, FTIR, UV-vis, and PL measurements, demonstrating favorable optical properties. The suitability of the fluorescent system to act as smart drug delivery system for cancer therapy was investigated by choosing gemcitabine (GMC) as a model drug. The GMC inclusion inside the system was evaluated by experimental and computational studies which confirmed the formation of a 1:1 complex between beta-CD and GMC. The inclusion of GMC within the beta-CD cavity led to a marked enhancement in its water solubility. Biological tests conducted on A549 cells revealed high cell internalization (similar to 80 %) and low cytotoxicity (IC50 = 262.7 mu g mL(-1)) of the beta-CD-aza[5]helicene conjugate. The results obtained by exploiting the host-guest chemistry of beta-cyclodextrin combined with the unique photophysical properties of aza[5]helicene could pave the way for new anticancer therapies, by increasing the therapeutic index of anticancer agents endowed with poor solubility in water and characterized by systemic toxicity and, thanks to the fluorescent properties of the inserted probe, following their release into biological pathways.