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New Unsymmetrical Bisacridine Derivatives Noncovalently Attached to Quaternary Quantum Dots Improve Cancer Therapy by Enhancing Cytotoxicity toward Cancer Cells and Protecting Normal Cells
Abstract
The use of nanoparticles for the controlled drug delivery to cells has emerged as a good alternative to traditional systemic delivery. Quantum dots (QDs) offer potentially invaluable societal benefits such as drug targeting and in vivo biomedical imaging. In contrast, QDs may also pose risks to human health and the environment under certain conditions. Here, we demonstrated that unique combination of nanocrystals core components (Ag-In-Zn-S) would eliminate the toxicity problem and increases their biomedical applications. The alloyed quaternary nanocrystals Ag-In-Zn-S (QDgreen: Ag1.0In1.2Zn5.6S9.4 and QDred: Ag1.0In1.0Zn1.0S3.5) were used to transport new unsymmetrical bisacridine derivatives (UAs: C-2028 and C-2045) into lung H460 and colon HCT116 cancer cells for improving the cytotoxic and antitumor action of these compounds. UAs were coupled with QD through physical adsorption. The obtained results clearly indicate that the synthesized nanoconjugates exhibited higher cytotoxic activity than unbound compounds, especially towards lung H460 cancer cells. Importantly, unsymmetrical bisacridines non-covalently attached to QD strongly protect normal cells from the drug action. It is worth to point out that QDgreen or QDred without UAs did not influence the growth of cancer as well as normal cells what is consistent with in vivo results. In non-cellular systems, at pH 5.5 and 4.0, which relates to the conditions of endosomes and lysosomes, the UAs released from QD-UAs nanoconjugates. An increase of total lysosomes content was observed in H460 cells treated with QDs-UAs what can affect the release of the UAs from the conjugates. Moreover, confocal laser scanning microscopy analyses revealed that QD-UAs nanoconjugates enter to H460 cells more efficiently than to HCT116 and normal cells, which may be the reason of their higher cytotoxicity against lung cancer. Summarizing, the non-covalent attachment of UAs to QDs increases the therapeutic efficiency of UAs, by improving cytotoxicity toward lung H460 cancer cells and having protecting effects on normal cells.
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Authors (7)
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Edyta Matysiak-Brynda
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Agata Kowalczyk
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Piotr Bujak
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Anna M. Nowicka
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Details
- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
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ACS Applied Materials & Interfaces
no. 12,
pages 17276 - 17289,
ISSN: 1944-8244 - Language:
- English
- Publication year:
- 2020
- Bibliographic description:
- Pilch J., Matysiak-Brynda E., Kowalczyk A., Bujak P., Mazerska Z., Nowicka A. M., Augustin E.: New Unsymmetrical Bisacridine Derivatives Noncovalently Attached to Quaternary Quantum Dots Improve Cancer Therapy by Enhancing Cytotoxicity toward Cancer Cells and Protecting Normal Cells// ACS Applied Materials & Interfaces -Vol. 12,iss. 15 (2020), s.17276-17289
- DOI:
- Digital Object Identifier (open in new tab) 10.1021/acsami.0c02621
- Sources of funding:
- Verified by:
- Gdańsk University of Technology
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