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Tumor Discovery Dual-targeting of cancer receptors by nanoparticles

Table 1. Real‑time polymerase chain reaction analysis of mRNA levels of apoptotic genes in MDA‑MB‑231 cells
Control Fe O ‑DPN‑HA‑FA‑TMX NPs Fe O ‑DPN‑HA‑FA Free TMX
3 4 3 4
Bclx 1 0.14 0.89 1.15
Bak1 1 9.58 0.045 0.18
Caspase-3 1 471.71 1.097 0.01
Values expressed using relative quantification which is equal with 2 -∆∆CT . The Bak1/Bclx ratios for Fe O -DPN-HA-FA-TMX NPs, Fe O -DPN-HA-FA
4
4
3
3
NPs, and free TMX were 68.43, 0.05, and 0.16, respectively
examined the effect of FA on the downregulation of Bclx Bak1, Bclx, and caspase-3 in MDA-MB-231 cell lines, it
and upregulation of the Bak1 expression in MCF-7 cells can be concluded that the presence of targeting agents on
and concluded that a cis-platinum complex containing FA the surface of nanocarriers and active targeting of cancer
can significantly increase Bak1/Bclx ratios compared with cells can be a useful step in the treatment of breast cancer
cisplatin alone . All these data indicate that the presence with TMX.
[41]
of FA along with anticancer drugs may play an important
role in increasing the apoptosis rate. 4. Conclusion
Therefore, we speculate that the conjugation of targeting ERα+ breast cancer cells like MDA-MB-231 may be
agents on NPs can affect the expression of apoptotic genes. resistant to treatments; therefore, TMX cannot induce
For these reasons, a dual-targeting nanocarrier containing apoptosis in this cell line. However, it is confirmed that the
HA and FA was synthesized for delivery of TMX to addition of FA to chemotherapy drugs can significantly
MDA-MB-231 breast cancer cells, and the ability of it in increase the expression of some genes associated with
the expression of Bclx, Bak1, and Caspase-3 was evaluated apoptosis. Accordingly, the targeted MNPs containing FA
utilizing RT-qPCR. Since Bcl-2 protein family is the key and HA were synthesized to improve the efficacy of TMX.
regulator of apoptosis, the investigation on them can MTT assay was done to show that modified MNPs have
provide detailed understanding about the mitochondria- the ability to reduce the cell viability of MDA-MB-231
mediated apoptotic pathway . The antiapoptotic proteins breast cancer cells. Furthermore, RT-PCR demonstrated
[42]
of this family that includes Bcl-2 and Bclx control a critical that Fe O -DPN-HA-FA-TMX NPs could upregulate the
4
3
step in commitment to apoptosis and prevent apoptosis, expression of Bak1 genes and downregulate the expression
while some pro-apoptotic members, such as Bax and Bak, of Bclx genes compared with TMX alone. All obtained
act to promote apoptosis . Table 1 demonstrates the results prove that the presence of targeting agents and
[43]
upregulation of Bak1 genes and downregulation of Bclx smart delivery of TMX could improve drug efficacy and
genes during the treatment by Fe O -DPN-HA-FA-TMX trigger apoptosis in MDA-MB-231.
3
4
NPs. Acknowledgments
As shown in Table 1, Fe O -DPN-HA-FA-TMX NPs
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4
have significantly increased the expression level of the The author thanks the Deputy of Research and Technology
Bak1 gene compared with free TMX, and also Fe O - of Zabol University of Medical Sciences for all supports
4
3
DPN-HA-FA NPs (P < 0.05), and these findings well provided.
demonstrated the ability of modified MNPs containing FA Funding
and HA in inducing apoptosis.
The caspase-3 can be activated through the intrinsic No financial support or grants received.
and extrinsic apoptotic pathways and its activation can Conflict of interest
be used to confirm the induction of apoptosis pathway
in MDA-MB-231 cell lines. Table 1 illustrates that Fe O - No conflicts of interest were reported by the author.
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DPN-HA-FA-TMX NPs increase the levels of caspase-3
associated with apoptosis, therefore highlighting the Author contributions
possible relation of Bak1/Bclx ratios with the apoptosis Mostafa Heidari Majd is the sole author of this paper and is
coordination enzyme, caspase-3. It is suggested that the responsible for every aspect of the work.
activation of caspase-3 is related to the mitochondrial
(intrinsic) pathway sensitive to Bak1 . Ethical statements
[44]
While Fe O -DPN-HA-FA NPs and free TMX alone This study was approved by the ethical committee of Zabol
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did not affect the mRNA expression or protein levels of University of Medical Sciences (IR.ZBMU.REC.1397.122).
Volume 1 Issue 1 (2022) 7 https://doi.org/10.36922/td.v1i1.41