AT G C showed similar cytotoxicity in HeLa cells when
AT11 G4-C5 showed similar cytotoxicity in HeLa Aminooxyacetic Acid when com-pared with free C5. However, complex formation greatly reduced the toxicity of the C5 ligand towards NHDF cells. Similar eﬀect occurred in the case of AT11-B0 G4-C5, although its cytotoxicity towards the cancer cell line was also reduced (47% of cell viability).
The results obtained for C8 were not so encouraging as those above discussed for the congener C3 and C5. In fact, the C8-complexes induce lower cytotoxicity towards malignant cells than free C8. In the case of AT11-B0 G4 this may be due to decreased internalization of the com-plex when compared to free C8 as suggested by the flow cytometry results. Indeed, when compared to AT11-C8, the AT11-B0-C8 complex showed a highest cytotoxicity reduction in HeLa cells relatively to free C8. By contrast, AT11 G4-C8 and AT11-B0 G4-C8 showed a rather si-milar cytotoxicity against non-malignant NHDF cells, which is quite comparable to the cytotoxicity exhibited by free C8 in the same cell line. International Journal of Pharmaceutics 568 (2019) 118511
Herein we reported a non-covalent conjugation approach between AT11 and AT11-B0 G4 and acridine orange derivatives in order to promote their selective delivery into HeLa cervical cancer cells. The resulting complexes were studied by circular dichroism, UV and fluor-escence spectroscopies. The serum stability of the complexes versus free DNA was also determined. Additionally, the aptamers and their con-jugates were tested in a cellular environment to assess their nucleolin binding potential, cell penetration ability and cytotoxic eﬀect against HeLa cancer and healthy cells. The results showed that the interaction of the acridine derivatives with the aptamers is characterized by a medium-high aﬃnity (KD values in the 10−6–10−7 M range), leading to the stabilization of their G4 structure (> 10 °C for all ligands). The formation of supramolecular complexes reduced the cytotoxicity of the free ligands towards non-malignant cells. Additionally, both AT11 and AT11-B0 seemed to bind nucleolin on the cell surface of HeLa cells, as suggested by the colocalization experiments using anti-nucleolin anti-body.
In summary, the complexes AT11 G4-C3, AT11 G4-C5, AT11-B0 G4-C3 and AT11-B0 G4-C5 seem more promising candidates as therapeutic tools for cervical cancer than the C8 congeners. Eventually, this trend might reflect the highest stability of the complexes AT11 G4-C8 and AT11-B0 G4-C8 that can hinder the intracellular release of C8 to exert its therapeutic action. Our results emphasize the potential of using G4-aptamers as drug delivery systems for cervical cancer.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influ-ence the work reported in this paper.
J. Carvalho acknowledges a doctoral fellowship grant from the FCT
Appendix A. Supplementary data
J. Figueiredo, et al.
development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer.
specific binding to targets in cancer cells. J. Biomed. Biotechnol. 2010. https://doi.
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Aspirin inhibits hypoxia-mediated lung cancer cell stemness and exosome T function
Jinghua Chena,b, Ruilian Xub, Junxian Xiab, Jiacheng Huangb, Binbin Suc, Senming Wanga,
a Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China