Superparamagnetic iron oxide nanoparticles conjugated with folic acid for dual target-specific drug delivery and MRI in cancer theranostics

Mater Sci Eng C Mater Biol Appl. 2017 Jan 1;70(Pt 1):763-771. doi: 10.1016/j.msec.2016.09.052. Epub 2016 Sep 26.

Abstract

Monodispersed SPIONs (superparamagnetic iron oxide nanoparticles) co-coated with PEG and PEI polymers were prepared by an improved polyol method. To accomplish cancer-specific targeting properties, FA (folic acid) was then modified on the SPIONs via EDC/NHS method (FA-SPIONs). Doxorubicin (DOX) as an example anticancer drug was loaded within FA-SPIONs (DOX@FA-SPIONs), the DOX release rate of DOX@FA-SPIONs was much high in low pH PBS. The SPIONs, FA-SPIONs and DOX@FA-SPIONs with mean hydrodynamic diameters of 23, 40 and 67nm, respectively, performed excellent colloidal stability in PBS. Confocal laser scanning microscope (CLSM) study implicates that the DOX@FA-SPIONs target MCF-7 cells efficiently through the FA receptor-mediated endocytosis. DOX@FA-SPIONs were tested in nude mice with xenograft MCF-7 breast tumor though tail intravenous injection and were found inhibiting tumor growth more efficiently. The application of a magnetic field (MF) greatly improved the growth inhibiting efficiencies of DOX@FA-SPIONs on MCF-7 cells in vitro and on xenograft MCF-7 breast tumor of nude mice in vivo. The aggregation of SPIONs in tumor was monitored by magnetic resonance imaging (MRI) as the DOX@FA-SPIONs exhibited high r2 relaxivity (81.77mM-1S-1). Histology on liver, Lung, kidney and heart in mice showed no significant toxicity of DOX@FA-SPIONs on mice organs after 35-day treatment. The FA-SPIONs are a high efficient drug delivery nanoplatform for advanced cancer theranostics.

Keywords: Folic acid; MRI; Magnetic field; SPIONs; Theranostics.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Death / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dextrans / chemistry*
  • Doxorubicin / pharmacology
  • Drug Delivery Systems*
  • Female
  • Folic Acid / chemistry*
  • Humans
  • Hydrodynamics
  • Hydrogen-Ion Concentration
  • MCF-7 Cells
  • Magnetic Resonance Imaging*
  • Magnetite Nanoparticles / chemistry*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Neoplasms / diagnosis*
  • Neoplasms / therapy*
  • Particle Size
  • Surface Properties
  • Theranostic Nanomedicine / methods*
  • Tissue Distribution / drug effects

Substances

  • Antineoplastic Agents
  • Dextrans
  • Magnetite Nanoparticles
  • Doxorubicin
  • Folic Acid
  • ferumoxides