Increasing DNA binding affinity of doxorubicin by loading on Fe3O4 nanoparticles: A multi-spectroscopic study

Spectrochim Acta A Mol Biomol Spectrosc. 2020 Mar 15:229:117985. doi: 10.1016/j.saa.2019.117985. Epub 2019 Dec 24.

Abstract

Magnetic Fe3O4 nanoparticles were synthesized successfully by co-precipitation method and characterized using XRD, SEM and EDS analyses. Then doxorubicin (DOX, a known anticancer drug) was loaded onto nanoparticles. In vitro DNA interaction of free DOX and loaded DOX onto Fe3O4 nanoparticles (DOX-Fe3O4) was investigated by DNA-viscosity measurements, UV-visible and fluorescence spectroscopies. The obtained values for binding constant of DOX and DOX-Fe3O4 compounds from UV-visible spectroscopies were 0.04 × 105 and 0.68 × 105 L mol-1, respectively, which confirms DOX-Fe3O4 compound have a stronger interaction with CT-DNA compared to DOX. Considerable changes on viscosity of the compounds recommended that their binding mode with CT-DNA is intercalative binding. Fluorescence intensity of DOX and DOX-Fe3O4 was quenched via static process by regular addition of CT-DNA. Thermodynamic parameters suggest that Van der Waals forces and hydrogen bonding for DOX and electrostatic forces for DOX-Fe3O4 are predominantly responsible for interaction with CT-DNA. Competition fluorescence studies were done by Hoechst 33258 as a well-known groove binder and ethidium bromide (EtBr) as a known intercalator probe. Percentage of displacement for EtBr-DNA complex with DOX and DOX-Fe3O4 was 39% and 61%, and for Hoechst-DNA complex was 9% and 5%, respectively. These results confirmed that both compounds are intercalator binders, although DOX-Fe3O4 with a further 22% displacement is a stronger intercalator binder than DOX. The stronger interaction of DOX-Fe3O4 compared to DOX suggests that the current system can be used as a new and effective way to targeted therapy of anticancer drugs.

Keywords: DNA interaction; Doxorubicin; Fe(3)O(4) nanoparticles; Intercalative binding.

MeSH terms

  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / metabolism*
  • DNA / chemistry
  • DNA / metabolism*
  • Doxorubicin / chemistry
  • Doxorubicin / metabolism*
  • Ethidium / analogs & derivatives
  • Ferric Compounds / chemistry*
  • Humans
  • Magnetite Nanoparticles / chemistry*
  • Spectrometry, Fluorescence / methods*

Substances

  • Antibiotics, Antineoplastic
  • Ferric Compounds
  • Magnetite Nanoparticles
  • ethidium-DNA complex
  • ferric oxide
  • Doxorubicin
  • DNA
  • Ethidium