Folic acid on iron oxide nanoparticles: platform with high potential for simultaneous targeting, MRI detection and hyperthermia treatment of lymph node metastases of prostate cancer

Dalton Trans. 2017 Sep 26;46(37):12692-12704. doi: 10.1039/c7dt02139a.

Abstract

The overexpression of the folate receptor in most cancers has been widely exploited to specifically deliver folic acid (FA) coupled nanomedicines to tumors. However, complex coupling chemistry is often used to bind FA to the nanoparticles. Furthermore, very little has been reported for the targeting of nanomedicines to lymph node metastases (LNMs) of prostate cancer. We here report the simple and aqueous coating of iron oxide nanoparticles (IONPs) with FA for theranostics of LNMs of prostate cancer. FA was directly bound to the IONPs' surface without the use of any linker, simultaneously playing the role of the coating molecule and targeting agent. We measured for FA-IONPs a hydrodynamic diameter around 100 nm and a negative surface charge, what is needed to access and to be retained in the lymphatic system for the LNMs targeting. We also show that FA-IONPs are specifically uptaken by prostate cancer cells expressing the prostate specific membrane antigen, including LNMs cells. FA-IONPs also displayed both high relaxivity for MRI detection and high specific absorption rate needed for hyperthermia treatment of tumors. Our study provides a theranostic platform for targeting LNMs of prostate cancer with high potential for their detection by MRI and treatment by hyperthermia.

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Ferric Compounds / chemistry*
  • Folic Acid / chemistry*
  • Humans
  • Hyperthermia, Induced*
  • Lymph Nodes / diagnostic imaging
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Magnetic Resonance Imaging
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / therapeutic use
  • Magnetite Nanoparticles / toxicity
  • Male
  • Microscopy, Electron, Transmission
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Ferric Compounds
  • Magnetite Nanoparticles
  • ferric oxide
  • Folic Acid