TARGETING CYCLIN B1 WITH ANTISENSE OLIGONUCLETOTIDES- COATED SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES

  • Hosam Zaghloul Clinical Pathology Department, Faculty of Medicine, Mansoura University, Egypt
  • Doaa A. Shahin Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Egypt
  • Ibrahim El- Dosoky Pathology Department, Faculty of Medicine, Mansoura University, Egypt
  • Mahmoud E. El-awady Zoology Department, Faculty of Science, Mansoura University, Egypt
  • Fardous F. El-Senduny Chemistry Department, Faculty of Science, Mansoura University, Egypt
  • Nashwa K. Abousamra Clinical Pathology Department, Faculty of Medicine, Mansoura University, Egypt
  • Farid A. Badria Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Egypt

Abstract

Antisense oligonucleotides (ASO) represent an attractive trend as specific targeting molecules but sustain poor cellular uptake meanwhile superparamagnetic iron oxide nanoparticles (SPIONs) offer stability of ASO and improved cellular uptake. In the present work we aimed to functionalize SPIONs with ASO targeting the mRNA of Cyclin B1 which represents a potential cancer target and to explore its anticancer activity. For that purpose, four different SPIONs-ASO conjugates, S-M (1–4), were designated depending on the sequence of ASO and constructed by crosslinking carboxylated SPIONs to amino labeled ASO. The impact of S-M (1–4) on the level of Cyclin B1, cell cycle, ROS and viability of the cells were assessed by flowcytometry. The results showed that S-M3 and S-M4 reduced the level of Cyclin B1 by 35 and 36%, respectively. As a consequence to downregulation of Cyclin B1, MCF7 cells were shown to be arrested at G2/M phase (60.7%). S-M (1–4) led to the induction of ROS formation in comparison to the untreated control cells. Furthermore, S-M (1–4) resulted in an increase in dead cells compared to the untreated cells and SPIONs-treated cells. In conclusion, targeting Cyclin B1 with ASO-coated SPIONs may represent a specific biocompatible anticancer strategy.
Published
2018-10-24
How to Cite
Zaghloul, H., Shahin, D. A., Dosoky, I. E.-, El-awady, M. E., El-Senduny, F. F., Abousamra, N. K., & Badria, F. A. (2018). TARGETING CYCLIN B1 WITH ANTISENSE OLIGONUCLETOTIDES- COATED SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES. Journal of Drug Discovery And Therapeutics, 6(10). https://doi.org/https://doi.org/10.32553/jddt.v6i10.444
Section
Research Articles