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    Foliate-Targeting Quantum Dots-beta-Cyclodextrin Nanocarrier for Efficient Delivery of Unsymmetrical Bisacridines to Lung and Prostate Cancer Cells

    Year: 2022

    Journal: Int. J. Mol. Sci., Volume 23, FEB

    Authors: Pilch, Joanna; Kowalik, Patrycja; Kowalczyk, Agata; Bujak, Piotr; Kasprzak, Artur; Paluszkiewicz, Ewa; Augustin, Ewa; Nowicka, Anna M.

    Organizations: National Science Center, Poland [2020/37/N/NZ7/01979]; [POWR.03.02.00-00-I007/16-00 (POWER 2014-2020)]

    Keywords: folic acid; unsymmetrical bisacridines; quantum dots; cellular uptake; mechanism of internalization; drug delivery

    Targeted drug delivery by nanocarriers molecules can increase the efficiency of cancer treatment. One of the targeting ligands is folic acid (FA), which has a high affinity for the folic acid receptors, which are overexpressed in many cancers. Herein, we describe the preparation of the nanoconjugates containing quantum dots (QDs) and beta-cyclodextrin (beta-CD) with foliate-targeting properties for the delivery of anticancer compound C-2028. C-2028 was bound to the nanoconjugate via an inclusion complex with beta-CD. The effect of using FA in QDs-beta-CD(C-2028)-FA nanoconjugates on cytotoxicity, cellular uptake, and the mechanism of internalization in cancer (H460, Du-145, and LNCaP) and normal (MRC-5 and PNT1A) cells was investigated. The QDs-beta-CD(C-2028)-FA were characterized using DLS (dynamic light scattering), ZP (zeta potential), quartz crystal microbalance with dissipation (QCM-D), and UV-vis spectroscopy. The conjugation of C-2028 with non-toxic QDs or QDs-beta-CD-FA did not change the cytotoxicity of this compound. Confocal microscopy studies proved that the use of FA in nanoconjugates significantly increased the amount of delivered compound, especially to cancer cells. QD(green)-beta-CD(C-2028)-FA enters the cells through multiple endocytosis pathways in different levels, depending on the cell line. To conclude, the use of FA is a good self-navigating molecule in the QDs platform for drug delivery to cancer cells.
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