Design, synthesis, and evaluation of chitosan conjugated GGRGDSK peptides as a cancer cell-targeting molecular transporter

Naglaa S. El-Sayed, Amir N. Shirazi, Magda G. El-Meligy, Ahmed K. El-Ziaty, Zenat A. Nagieb, Keykavous Parang, Rakesh K. Tiwari

Research output: Contribution to journalArticlepeer-review

Abstract

Targeting cancer cells using integrin receptor is one of the promising targeting strategies in drug delivery. In this study, we conjugated an integrin-binding ligand (GGRGDSK) peptide to chitosan oligosaccharide (COS) using sulfo-SMCC as a bifunctional linker to afford COS-SMCC-GGRGDSK. The conjugated polymer was characterized by FT-IR, 1H NMR, 13C NMR, and SEM. COS-SMCC-GGRGDSK did not show cytotoxicity up to a concentration of 1 mg/mL in the human leukemia cell line (CCRF-CEM). The conjugate was evaluated for its ability to enhance the cellular uptake of a cell-impermeable cargo (e.g., F'-G(pY)EEI phosphopeptide) in CCRF-CEM, and human ovarian carcinoma (SK-OV-3) cancer cell lines. Additionally, RGD modified and unmodified COS polymers were used to prepare nanoparticles by ionic gelation and showed particle size ranging from 187 to 338 nm, and zeta potential of 12.2-18.3 mV using dynamic light scattering. The efficiency of COS-NPs and COS-SMCC-RGDSK NPs was assayed for translocation of two synthetic cytotoxic agents ((2-(2-aminoethylamino)-4-(4-chlorophenyl)-6-(1H-indol-3-yl) nicotinonitrile (ACIN), and 2-(2-aminoethylamino)-6-(1H-indol-3-yl)-4-(4-methoxyphenyl)-nicotinonitrile (AMIN)) into CCRF-CEM and human prostate (DU-145) cancer cell lines. The results showed a dramatic reduction in the cell viability on their treatment with RGD targeted COS NPs in comparison to paclitaxel (PTX), free drug, and drug-loaded COS NPs.

Original languageEnglish (US)
Pages (from-to)611-622
Number of pages12
JournalInternational Journal of Biological Macromolecules
Volume87
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Keywords

  • Cancer cell lines
  • Chitosan oligosaccharide
  • GGRGDSK peptide
  • Ionic gelation
  • Phosphopeptide
  • Sulfo-SMCC linker

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Structural Biology

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