PEGylated mesoporous silica core-shell redox-responsive nanoparticles for delivering paclitaxel to breast cancer cells

Int J Pharm. 2024 Apr 25:655:124024. doi: 10.1016/j.ijpharm.2024.124024. Epub 2024 Mar 26.

Abstract

Controlling the drug release and restricting its presence in healthy organs is extremely valuable. In this study, mesoporous silica nanoparticles (MSN) as the core, loaded with paclitaxel (PTX), were coated with a non-porous silica shell functionalized with disulfide bonds. The nanoparticles were further coated with polyethylene glycol (PEG) via disulfide linkages. We analyzed the physicochemical properties of nanoparticles, including hydrodynamic size via Dynamic Light Scattering (DLS), zeta potential, X-ray Diffraction (XRD) patterns, Fourier-Transform Infrared (FTIR) spectra, and imaging through Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). The drug release profile in two distinct glutathione (GSH) concentrations of 2 µM and 10 µM was measured. The cellular uptake of nanoparticles by MCF-7 cell line was determined using Confocal Laser Scanning Microscopy (CLSM) images and flow cytometry. Furthermore, the cell viability and the capability of nanoparticles to induce apoptosis in MCF-7 cell line were studied using the MTT assay and flow cytometry, respectively. Our investigations revealed that the release of PTX from the drug delivery system was redox-responsive. Also, results indicated an elevated level of cellular uptake and efficient induction of apoptosis, underscoring the promising potential of this redox-responsive drug delivery system for breast cancer therapy.

Keywords: Cancer treatment; Controlled release; Core–shell nanoparticle; Drug delivery; Mesoporous silica nanoparticle; Redox-responsive.

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Disulfides
  • Drug Carriers / chemistry
  • Drug Delivery Systems
  • Female
  • Glutathione / chemistry
  • Humans
  • Nanoparticles* / chemistry
  • Oxidation-Reduction
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Polyethylene Glycols / chemistry
  • Porosity
  • Silicon Dioxide / chemistry

Substances

  • Paclitaxel
  • Silicon Dioxide
  • Polyethylene Glycols
  • Glutathione
  • Disulfides
  • Drug Carriers