cRGD-functionalized, DOX-conjugated, and ⁶⁴Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging

Biomaterials. 2011 Jun;32(17):4151-60. doi: 10.1016/j.biomaterials.2011.02.006. Epub 2011 Mar 2.


Multifunctional and water-soluble superparamagnetic iron oxide (SPIO) nanocarriers were developed for targeted drug delivery and positron emission tomography/magnetic resonance imaging (PET/MRI) dual-modality imaging of tumors with integrin α(v)β₃ expression. An anticancer drug was conjugated onto the PEGylated SPIO nanocarriers via pH-sensitive bonds. Tumor-targeting ligands, cyclo(Arg-Gly-Asp-d-Phe-Cys) (c(RGDfC)) peptides, and PET ⁶⁴Cu chelators, macrocyclic 1,4,7-triazacyclononane-N, N', N″-triacetic acid (NOTA), were conjugated onto the distal ends of the PEG arms. The effectiveness of the SPIO nanocarriers as an MRI contrast agent was evaluated via an in vitro r₂ MRI relaxivity measurement. cRGD-conjugated SPIO nanocarriers exhibited a higher level of cellular uptake than cRGD-free ones in vitro. Moreover, cRGD-conjugated SPIO nanocarriers showed a much higher level of tumor accumulation than cRGD-free ones according to non-invasive and quantitative PET imaging, and ex vivo biodistribution studies. Thus, these SPIO nanocarriers demonstrated promising properties for combined targeted anticancer drug delivery and PET/MRI dual-modality imaging of tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Contrast Media / chemistry
  • Dextrans / chemical synthesis*
  • Diagnostic Imaging / methods*
  • Doxorubicin / pharmacokinetics*
  • Drug Carriers / chemical synthesis*
  • Drug Delivery Systems
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Integrin alphaVbeta3 / metabolism
  • Magnetic Resonance Imaging
  • Magnetite Nanoparticles
  • Malonates / chemical synthesis
  • Mice
  • Mice, Nude
  • Models, Animal
  • Nanomedicine / methods
  • Neoplasms / drug therapy
  • Particle Size
  • Peptides, Cyclic / chemistry
  • Positron-Emission Tomography
  • Tissue Distribution


  • Contrast Media
  • Dextrans
  • Drug Carriers
  • Integrin alphaVbeta3
  • Magnetite Nanoparticles
  • Malonates
  • Peptides, Cyclic
  • monoethyl malonate
  • Doxorubicin
  • ferumoxides