New
Unsymmetrical Bisacridine Derivatives Noncovalently Attached to Quaternary
Quantum Dots Improve Cancer Therapy by Enhancing Cytotoxicity toward
Cancer Cells and Protecting Normal Cells
posted on 2020-04-01, 18:07authored byJoanna Pilch, Edyta Matysiak-Brynda, Agata Kowalczyk, Piotr Bujak, Zofia Mazerska, Anna M. Nowicka, Ewa Augustin
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.