New Unsymmetrical Bisacridine Derivatives Noncovalently Attached to Quaternary Quantum Dots Improve Cancer Therapy by Enhancing Cytotoxicity toward Cancer Cells and Protecting Normal Cells

Joanna Pilch , Edyta Matysiak-Brynda , Agata Kowalczyk , Piotr Bujak , Zofia Mazerska , Anna M. Nowicka , Ewa Augustin

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 a unique combination of nanocrystals core components (Ag-In-Zn-S) would eliminate the toxicity problem and increase their biomedical applications. The alloyed quaternary nanocrystals Ag-In-Zn-S (QDgreen, Ag1.0In1.2Zn5.6S9.4; 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 toward lung H460 cancer cells. Importantly, unsymmetrical bisacridines noncovalently attached to QD strongly protect normal cells from the drug action. It is worth pointing out that QDgreen or QDred without UAs did not influence the growth of cancer and normal cells, which is consistent with in vivo results. In noncellular systems, at pH 5.5 and 4.0, which relates to the conditions of endosomes and lysosomes, the UAs were released from QD-UAs nanoconjugates. An increase of total lysosomes content was observed in H460 cells treated with QDs-UAs which can affect the release of the UAs from the conjugates. Moreover, confocal laser scanning microscopy analyses revealed that QD-UAs nanoconjugates enter H460 cells more efficiently than to HCT116 and normal cells, which may be the reason for their higher cytotoxicity against lung cancer. Summarizing, the noncovalent 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.

Author Joanna Pilch - [Gdańsk University of Technology (PG)]
Joanna Pilch,,
-
- Politechnika Gdańska
, Edyta Matysiak-Brynda - [Faculty of Chemistry (WChUW) [University of Warsaw (UW)]]
Edyta Matysiak-Brynda,,
-
- Wydział Chemii
, Agata Kowalczyk - Faculty of Chemistry (WChUW) [University of Warsaw (UW)]
Agata Kowalczyk,,
-
, Piotr Bujak (FC / CPCT)
Piotr Bujak,,
- Chair Of Polymer Chemistry And Technology
, Zofia Mazerska - [Gdańsk University of Technology (PG)]
Zofia Mazerska,,
-
- Politechnika Gdańska
, Anna M. Nowicka - Faculty of Chemistry (WChUW) [University of Warsaw (UW)]
Anna M. Nowicka,,
-
, Ewa Augustin - [Gdańsk University of Technology (PG)]
Ewa Augustin,,
-
- Politechnika Gdańska
Journal seriesACS Applied Materials & Interfaces, ISSN 1944-8244, e-ISSN 1944-8252
Issue year2020
Vol12
Pages17276-17289
Keywords in English unsymmetrical bisacridine derivatives Ag-In-Zn-S nanocrystals lung and colon cancer cells drug-carrier degradation pathway cytotoxic activity in vivo antitumor efficacy pH-dependent release cellular uptake
ASJC Classification2500 General Materials Science
DOIDOI:10.1021/acsami.0c02621
URL https://pubs.acs.org/doi/10.1021/acsami.0c02621
Languageen angielski
File
acsami.0c02621.pdf 9.47 MB
Score (nominal)200
Score sourcejournalList
ScoreMinisterial score = 200.0, 04-08-2020, ArticleFromJournal
Publication indicators Scopus Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.539; WoS Impact Factor: 2018 = 8.456 (2) - 2018=8.694 (5)
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