Fabrication and intracellular delivery of siRNA/carbonate apatite nano-composites for effective knockdown of cyclin B1 gene

  • Anthony Stanislaus | ezharul_chowdhury@imu.edu.my Monash University, Malaysia.
  • Sharif Hossain
  • Ming Jang Chua
  • Anil Philip Kunnath
  • Quek Chia Wen
  • Sharifah Nur Syakira
  • Gan Yew Siong
  • Siong Wei Loong
  • Iekhsan Othman
  • Toshihiro Akaike
  • Ezharul Hoque Chowdhury

Abstract

Gene therapy through intracellular delivery of a functional gene or a gene-silencing element is a promising approach to properly treat critical human diseases like cancer. The ability of synthetically designed small interfering RNA (siRNA) to effectively silence genes at post-transcriptional level has made them attractive options in targeted therapeutics. However, naked siRNA being unable to passively diffuse through cellular membranes, poses difficulty in fully exploiting the potential of the technology. pH-sensitive carbonate apatite has been developed as an efficient tool to deliver siRNA into the mammalian cells by virtue of its high affinity interaction with the siRNA and effective cellular endocytosis. Moreover, internalized siRNA has been found to escape from the endosomes in a time-dependent manner and effectively silenced reporter gene expression. Knockdown of cyclin B1 gene with only 10 nM of siRNA delivered by carbonate apatite has resulted in significant death of cervical cancer cells. Moreover, delivery of siRNA against cyclin B1 gene has led to the sensitization of the cancer cells to both cisplatin and doxorubicin at a particulat drug concentration. Thus, the new method of siRNA delivery is highly promising for pre-clinical and clinical cancer therapy using siRNA therapeutics.

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Published
2011-07-08
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How to Cite
Stanislaus, A., Hossain, S., Chua, M. J., Kunnath, A. P., Wen, Q. C., Syakira, S. N., Siong, G. Y., Loong, S. W., Othman, I., Akaike, T., & Chowdhury, E. H. (2011). Fabrication and intracellular delivery of siRNA/carbonate apatite nano-composites for effective knockdown of cyclin B1 gene. Drugs and Therapy Studies, 1(1), e8. https://doi.org/10.4081/dts.2011.e8