Abstract

Quantum dots (QDs) are a novel class of semiconducting nanomaterials with unique properties, including drug delivery systems and biomedical applications. Unsymmetrical bisacridines (UAs), synthesized in our laboratory, patented in Europe [EP 3070078B1] and USA [US 10202349 B2], are a new class of antitumor agents highly active against many experimental cellular and tumor models, including lung, colon, pancreatic and prostate. Here, we investigated whether the conjugation of UAs with QDs has an impact on cytotoxicity and biological response against human lung H460 and colon HCT116 cancer cells, compared to UAs alone. UAs (C-2028 and C-2045) were non-covalently attached to the QDred/green (Ag-In-Zn-S/MUA). The externalization of phosphatidylserine, the decrease of mitochondrial transmembrane potential and the induction of senescence following QDs-UAs treatment at IC80 were examined. Our results indicate that QDs-UAs conjugates exhibited higher cytotoxic activity towards H460 cells than UAs alone, without altering HCT116 cells cytotoxicity. In both cell lines, studied compounds and their conjugates induced apoptotic cell death which reached a higher level in H460 than in HCT116 cells. Interestingly, the number of apoptotic cells (A+/PI+) significantly decreased since 72 h of QDs-C-2028 conjugates treatment compared to C-2028 alone in H460 and HCT116 cells. These results are consistent with the data from mitochondrial transmembrane potential. Furthermore, UAs induced cellular senescence in H460 cells (flattened cells, expression of -galactosidase) and this process was intensified following QDs-UAs conjugates treatment. Surprisingly, the senescence process was not observed in HCT116 cells. Summing up, QDs-UAs nanoconjugates enhanced the cytotoxicity and cellular senescence in H460 cells, but weaken the cellular response (QDs-C-2028) compared to C-2028 alone in both cell lines. These studies were supported by the National Science Center, Poland, UMO-2016/23/B/NZ7/03324.

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