Quantum Dots as a Good Carriers of Unsymmetrical Bisacridines for Modulating Cellular Uptake and the Biological Response in Lung and Colon Cancer Cells

Abstract

Nanotechnology-based drug delivery provides a promising area for improving the efficacy of cancer treatments. Therefore, we investigate the potential of using quantum dots (QDs) as drug carriers for antitumor unsymmetrical bisacridine derivatives (UAs) to cancer cells. We examine the influence of QD–UA hybrids on the cellular uptake, internalization (Confocal Laser Scanning Microscope), and the biological response (flow cytometry and light microscopy) in lung H460 and colon HCT116 cancer cells. We show the time-dependent cellular uptake of QD–UA hybrids, which were more efficiently retained inside the cells compared to UAs alone, especially in H460 cells, which could be due to multiple endocytosis pathways. In contrast, in HCT116 cells, the hybrids were taken up only by one endocytosis mechanism. Both UAs and their hybrids induced apoptosis in H460 and HCT116 cells (to a greater extent in H460). Cells which did not die underwent senescence more efficiently following QDs–UAs treatment, compared to UAs alone. Cellular senescence was not observed in HCT116 cells following treatment with both UAs and their hybrids. Importantly, QDgreen/red themselves did not provoke toxic responses in cancer or normal cells. In conclusion, QDs are good candidates for targeted UA delivery carriers to cancer cells while protecting normal cells from toxic drug activities.

c-Myc Protein Level Affected by Unsymmetrical Bisacridines Influences Apoptosis and Senescence Induced in HCT116 Colorectal and H460 Lung Cancer Cells

“…Additionally, UAs turned out to be very potent in inhibiting the growth of HCT116- and H460-derived spheroids [ 27 ]. Moreover, some of the UAs were conjugated with quantum dots (QDs), which improved their delivery to cancer cells [ 28 , 29 , 30 ]. In the presented study, we wanted to show the cellular mechanism of action of four UA derivatives in relation to changes in c-Myc and K-Ras proteins.…”

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

“…Here, we studied the influence of navigating molecules (folic acid) and incubation time (1, 24, 48, and 72 h). Based on our previous experience with cellular uptake studies [27], we selected for further experiments nanoconjugates with QD green . The amount of the delivered C-2028 compound to cancer cells was higher in the case of the use of QD green as a drug delivery platform compared to QD red .…”

“…We showed that the efficient procedure for the synthesis of QD−UA hybrids successfully increases the cytotoxic activity of UAs in cancer H460 cells and has protective effects on normal MRC-5 and CCD 841 CoN cells [25]. We investigated also the influence of conjugation of UAs with QDs on the cellular uptake and the biological response in lung H460 and colon HCT116 cancer cells as well as normal MRC-5 and CCD 841 CoN cells [25,27].…”

Acid–Base Equilibrium and Self-Association in Relation to High Antitumor Activity of Selected Unsymmetrical Bisacridines Established by Extensive Chemometric Analysis

“…Studies on the biological effects of these compounds demonstrated their ability to suppress 3D cancer spheroid growth [4]. Moreover, their anticancer activity was enhanced when bound to quaternary quantum dots, resulting in selective upregulation of their cellular uptake [5][6][7]. Our previous studies demonstrated that UAs undergo metabolic transformations which retain the compounds' dimeric structure.…”