Novel of nano delivery system for Linalool loaded on gold nanoparticles conjugated with CALNN peptide for application in drug uptake and induction of cell death on breast cancer cell line

Mater Sci Eng C Mater Biol Appl. 2019 Jan 1:94:949-964. doi: 10.1016/j.msec.2018.10.014. Epub 2018 Oct 13.

Abstract

Linalool is a monoterpene alcohol which occurs naturally in several aromatic plants. The aims of this study are to load Linalool on gold nanoparticles, conjugate the complex with CALNN peptide, and investigate them for in-vitro anticancer activities against breast cancer (MCF-7) cell line. Linalool was obtained with 98% purity while gold nanoparticles and CALNN peptide were chemically synthesized. The formation of LIN-GNPs and LIN-GNPs-CALNN was observed through a color change. These compounds were confirmed and characterized using SEM, DLS, AFM, UV-VIS spectrophotometer, XRD, and FTIR. The free radical scavenging potential of each compound was confirmed based on its stable antioxidant effects using different parameters. Blood compatibility on red blood cells was confirmed by hemolytic and in vitro cytotoxicity assays. The in-vitro anticancer activity of each compound towardMCF-7 cell line was investigated using various parameters. From the results, Linalool, GNPs, LIN-GNPs, and LIN-GNPs-CALNN were found to exert cell growth arrest against MCF-7 cell line. The anti-proliferative effect of these compounds was due to cell death and induction of apoptosis confirmed using acridine orange-Ethidium bromide dual staining, DAPI staining, and electrophoresis analysis of DNA fragmentation. High fluorescent signals specific for the cellular uptake of LIN-GNPs and LIN-GNPs-CALNN into the cytoplasm of the cell line were confirmed. To study the toxicity of LIN-GNPs-CALNN in animal models, the hematological, histopathological, and body weight changes were estimated after 4 weeks of intraperitoneal injection of the compounds into the animal models. Our results demonstrate that Linalool, GNPs, Linalool-GNPs, and Linalool-GNPs-CALNN peptide had no side effects and could be clinically used for future therapeutic purposes.

Keywords: Antioxidant activity; CALNN; Cellular uptake; Cytotoxicity; FTIC; Gold nanoparticles; Linalool; MCF-7.

MeSH terms

  • Acyclic Monoterpenes
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Antioxidants / pharmacology
  • Biphenyl Compounds / chemistry
  • Blood Cells / drug effects
  • Blood Cells / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Cell Death / drug effects
  • Cell Nucleus Shape
  • Cell Proliferation / drug effects
  • DNA Fragmentation / drug effects
  • Drug Delivery Systems*
  • Dynamic Light Scattering
  • Endocytosis
  • Female
  • Gold / chemistry*
  • Hemolysis / drug effects
  • Humans
  • Hydroxyl Radical / chemistry
  • MCF-7 Cells
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / ultrastructure
  • Mice, Inbred BALB C
  • Monoterpenes / pharmacology
  • Monoterpenes / therapeutic use*
  • Monoterpenes / toxicity
  • Peptides / chemistry*
  • Picrates / chemistry
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction

Substances

  • Acyclic Monoterpenes
  • Antineoplastic Agents
  • Antioxidants
  • Biphenyl Compounds
  • Monoterpenes
  • Peptides
  • Picrates
  • Hydroxyl Radical
  • Gold
  • linalool
  • 1,1-diphenyl-2-picrylhydrazyl