Cellular uptake and anti-tumor activity of gemcitabine conjugated with new amphiphilic cell penetrating peptides

Authors

  • Parvin Zakeri-Milani Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
  • Samad Mussa Farkhani Research Center for Pharmaceutical Nanotechnology and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  • Ali Shirani Research Center for Pharmaceutical Nanotechnology and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  • Samaneh Mohammadi Research Center for Pharmaceutical Nanotechnology and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  • Javid Shahbazi Mojarrad Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
  • Jafar Akbari Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
  • Hadi Valizadeh Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

DOI:

https://doi.org/10.17179/excli2017-249

Keywords:

cell penetrating peptide, gemcitabine, toxicity, drug delivery

Abstract

Gemcitabine (Gem) is used as a single agent or in combination with other anticancer agents to treat many types of solid tumors. However, it has many limitations such as a short plasma half-life, dose-limiting toxicities and drug resistance. Cell-penetrating peptides (CPPs) are short peptides which may deliver a large variety of cargo molecules into the cancerous cells. The current study was designed to evaluate the antiproliferative activity of gemcitabine chemically conjugated to CPPs. The peptides were synthesized using solid phase synthesis procedure. The uptake efficiency of CPPs into cells was examined by flow cytometry and fluorescent microscopy. The synthesized peptides were chemically conjugated to Gem and the in vitro cytotoxicity of conjugates was tested by MTT assay on A594 cell line. According to the obtained results, cellular uptake was increased with increasing the concentration of CPPs. On the other hand the coupling of Gem with peptides containing block sequence of arginine (R5W3R4) and some alternating sequences (i.e. [RW]6 and [RW]3) exhibited improved antitumor activity of the drug. The findings in this study support the advantages of using cell-penetrating peptides for improving intracellular delivery of Gem into tumor as well as its activity.

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Published

2017-05-09

How to Cite

Zakeri-Milani, P., Mussa Farkhani, S., Shirani, A., Mohammadi, S., Shahbazi Mojarrad, J., Akbari, J., & Valizadeh, H. (2017). Cellular uptake and anti-tumor activity of gemcitabine conjugated with new amphiphilic cell penetrating peptides. EXCLI Journal, 16, 650–662. https://doi.org/10.17179/excli2017-249

Issue

Vol. 16 (2017)

Section

Original articles

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