Electroporation and lipid nanoparticles with cyanine IR-780 and flavonoids as efficient vectors to enhanced drug delivery in colon cancer

Bioelectrochemistry. 2016 Aug:110:19-31. doi: 10.1016/j.bioelechem.2016.02.013. Epub 2016 Feb 27.

Abstract

Nanocarriers and electroporation (also named electropermeabilization) are convenient methods to increase drug transport. In the current study, we present an effective support of drug delivery into cancer cells, utilizing these methods. We compare the efficiency of each of them and their combination. Multifunctional solid lipid nanoparticles (SLNs) loaded with a cyanine-type IR-780 - acting as a diagnostic agent and a photosensitizer, and a flavonoid derivative - baicalein (BAI) or fisetin (FIS) as a therapeutic cargo - were fabricated via solvent-diffusion method. A therapy supplemented with flavonoids may provide a more precise method to apply desirable lower drug doses and is more likely to result in lower toxicity and a decrease in tumor growth. The SLNs were stabilized with Phospholipon 90G at various concentrations; cetyl palmitate (CP) was applied as a solid matrix. The obtained nanosystems were characterized by dynamic light scattering (size along with size distribution), UV-vis (cargos encapsulation efficiency) and atomic force microscopy (morphology and shape). The obtained SLNs were used as drug carriers alone and in combination with electropermeabilization induced by millisecond pulsed electric fields of high intensity. Two cell lines were selected for the study: LoVo and CHO-K1. The viability was assessed after electroporation alone, the use of electroporation and nanoparticles, and nanoparticles or drugs alone. The intracellular accumulation of cyanine IR-780 and the impact on intracellular structure organization of cytoskeleton was visualized with confocal microscopy method with alpha-actin and beta-tubulin. In this study, the efficacy of nanoparticles with mixed cargo, additionally enhanced by electroporation, is demonstrated to act as an anticancer modality to eliminate cancer cells.

Keywords: Electroporation; Flavonoids; Photodynamic reaction; Solid lipid nanoparticles.

MeSH terms

  • Animals
  • CHO Cells
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / pathology*
  • Cricetulus
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • Cytoskeleton / radiation effects
  • Drug Carriers / chemistry*
  • Electroporation*
  • Flavanones / chemistry
  • Flavanones / pharmacology
  • Flavanones / therapeutic use
  • Flavonoids / chemistry*
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use
  • Flavonols
  • Humans
  • Indoles / chemistry*
  • Nanoparticles / chemistry*
  • Palmitates / chemistry*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Superoxide Dismutase / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • 2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium
  • Drug Carriers
  • Flavanones
  • Flavonoids
  • Flavonols
  • Indoles
  • Palmitates
  • Photosensitizing Agents
  • Tumor Suppressor Protein p53
  • baicalein
  • cetyl palmitate
  • Superoxide Dismutase
  • fisetin