Synthesis, characterization, and cytotoxicity evaluation of dextran-myristoyl-ECGKRK peptide conjugate

Int J Biol Macromol. 2021 Nov 30:191:1204-1211. doi: 10.1016/j.ijbiomac.2021.09.160. Epub 2021 Sep 29.

Abstract

CGKRK is a well-known tumor homing peptide with significant specificity for many types of cancer tissues. Herein, we describe the synthesis of a novel drug delivery system based on dextran decorated with myristoyl-ECGKRK peptide. The myristoylated peptide was synthesized and conjugated to dextran via an ester bond followed by purification. FT-IR and NMR confirmed the success of the conjugation reaction, while the surface morphology examination revealed that the conjugate has a characteristic porous network-like structure. Dynamic-light scattering measurements indicated the ability of the conjugate to self-assemble into nanoparticles with an average size of 248 ± 6.33 nm, and zeta potential of 10.7 mV. The cytotoxicity profiles for the peptide, dextran (Dex0), and dextran-peptide conjugate (Dex1) were evaluated against triple-negative breast cancer cells (MDA-MB-231), breast cancer cells (MCF-7), and human embryonic normal kidney cells (HEK-293). The results revealed that myristoyl-ECGKRK was noncytotoxic on the two different breast cancer cell lines up to 50 μM, but the cell viability was minimally reduced to 85% at 50 μm in HEK-293 cells. Similarly, Dex0 showed a neglected cytotoxicity profile at all tested concentrations. The Dex1 was not toxic to the cells up to a concentration of 8.3 mg/mL.

Keywords: Breast cancer; Dextran; Tumor-targeting peptide.

MeSH terms

  • Breast Neoplasms / drug therapy
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dextrans / chemistry*
  • Dextrans / therapeutic use*
  • Drug Delivery Systems*
  • HEK293 Cells
  • Humans
  • MCF-7 Cells
  • Nanoparticles / chemistry
  • Peptides / chemistry*
  • Peptides / therapeutic use*
  • Spectroscopy, Fourier Transform Infrared
  • Triple Negative Breast Neoplasms / drug therapy

Substances

  • Dextrans
  • Peptides