Synthesis, Characterization, and in Vitro Testing of Superparamagnetic Iron Oxide Nanoparticles Targeted Using Folic Acid-Conjugated Dendrimers

Kevin J. Landmark,^†^,^# Stassi DiMaggio,^∇ Jesse Ward,^⊥ Christopher Kelly,^†^,^‡^,^¶^,^# Stefan Vogt, Seungpyo Hong,^§^,^# Alina Kotlyar,^# Andrzej Myc,^# Thommey P. Thomas,^# James E. Penner-Hahn,^‡^,^⊥ James R. Baker Jr.,^# Mark M. Banaszak Holl,^†^,^‡^,^§^,^⊥^,^#^,^¶^,^* and Bradford G. Orr^†^,^∥^,^#^,^*

^† Programs in Applied Physics, ^‡ Biophysics, ^§ Macromolecular Science and Engineering, ^⊥ Departments of Chemistry, ^∥ Physics, ^# the Michigan Nanotechnology Institute for Medicine and Biological Sciences, ^¶ Graham Environmental Sustainability Institute, The University of Michigan, Ann Arbor, Michigan 48109, ^∇ Department of Chemistry, Xavier University, New Orleans, Louisiana 70125, and X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne, Illinois 60439

^*Address correspondence to mbanasza@umich.edu, orr@umich.edu.

ABSTRACT

Organic-coated superparamagnetic iron oxide nanoparticles (OC-SPIONs) were synthesized and characterized by transmission electron microscopy and X-ray photoelectron spectroscopy. OC-SPIONs were transferred from organic media into water using poly(amidoamine) dendrimers modified with 6-TAMRA fluorescent dye and folic acid molecules. The saturation magnetization of the resulting dendrimer-coated SPIONs (DC-SPIONs) was determined, using a superconducting quantum interference device, to be 60 emu/g Fe versus 90 emu/g Fe for bulk magnetite. Selective targeting of the DC-SPIONs to KB cancer cells in vitro was demonstrated and quantified using two distinct and complementary imaging modalities: UV–visible and X-ray fluorescence; confocal microscopy confirmed internalization. The results were consistent between the uptake distribution quantified by flow cytometry using 6-TAMRA UV–visible fluorescence intensity and the cellular iron content determined using X-ray fluorescence microscopy.