Green Synthesized Montmorillonite/Carrageenan/Fe3O4 Nanocomposites for pH-Responsive Release of Protocatechuic Acid and Its Anticancer Activity

Int J Mol Sci. 2020 Jul 9;21(14):4851. doi: 10.3390/ijms21144851.

Abstract

Discovery of a novel anticancer drug delivery agent is important to replace conventional cancer therapies which are often accompanied by undesired side effects. This study demonstrated the synthesis of superparamagnetic magnetite nanocomposites (Fe3O4-NCs) using a green method. Montmorillonite (MMT) was used as matrix support, while Fe3O4 nanoparticles (NPs) and carrageenan (CR) were used as filler and stabilizer, respectively. The combination of these materials resulted in a novel nanocomposite (MMT/CR/Fe3O4-NCs). A series of characterization experiments was conducted. The purity of MMT/CR/Fe3O4-NCs was confirmed by X-ray diffraction (XRD) analysis. High resolution transmission electron microscopy (HRTEM) analysis revealed the uniform and spherical shape of Fe3O4 NPs with an average particle size of 9.3 ± 1.2 nm. Vibrating sample magnetometer (VSM) analysis showed an Ms value of 2.16 emu/g with negligible coercivity which confirmed the superparamagnetic properties. Protocatechuic acid (PCA) was loaded onto the MMT/CR/Fe3O4-NCs and a drug release study showed that 15% and 92% of PCA was released at pH 7.4 and 4.8, respectively. Cytotoxicity assays showed that both MMT/CR/Fe3O4-NCs and MMT/CR/Fe3O4-PCA effectively killed HCT116 which is a colorectal cancer cell line. Dose-dependent inhibition was seen and the killing was enhanced two-fold by the PCA-loaded NCs (IC50-0.734 mg/mL) compared to the unloaded NCs (IC50-1.5 mg/mL). This study highlights the potential use of MMT/CR/Fe3O4-NCs as a biologically active pH-responsive drug delivery agent. Further investigations are warranted to delineate the mechanism of cell entry and cancer cell killing as well as to improve the therapeutic potential of MMT/CR/Fe3O4-NCs.

Keywords: Fe3O4 nanocomposites; anticancer; carrageenan; drug delivery; iron oxide; montmorillonite; protocatechuic acid.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Bentonite / chemistry*
  • Carrageenan / chemistry*
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods
  • Drug Liberation / drug effects
  • Ferric Compounds / chemistry*
  • Ferrosoferric Oxide / chemistry
  • Green Chemistry Technology / methods
  • HCT116 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Hydroxybenzoates / chemistry*
  • Hydroxybenzoates / pharmacology
  • Magnetite Nanoparticles / chemistry
  • Nanocomposites / chemistry*
  • Particle Size

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Ferric Compounds
  • Hydroxybenzoates
  • Magnetite Nanoparticles
  • Bentonite
  • ferric oxide
  • protocatechuic acid
  • Carrageenan
  • Ferrosoferric Oxide