Preparation and Evaluation of a Radioisotope-Incorporated Iron Oxide Core/Au Shell Nanoplatform for Dual Modality Imaging

Abstract

Magnetic gold-coated iron oxide nanoparticles (Fe@Au NPs) have recently emerged as a new type of iron oxide nanoparticle based magnetic resonance imaging (MRI) contrast agents, in which the gold shell provides a conveniently tunable surface for the presentation of multiple functional molecules. Given the versatility of this nanoplatform and the intrinsic sensitivity limitation of MRI contrast agents, a new approach was developed in this work to incorporate radioisotopes with suitable half-lives into the iron oxide core of Fe@Au NPs and impart the superior sensitivity of nuclear imaging to the nanoplatform. The incorporation of 67Ga was successfully accomplished by co-precipitation of 67Ga3+ with Fe3+/Fe2+ ions at a pH ranging from 4–10. The gold coating procedure was carried out by an iterative hydroxylamine seeding process. Upon the gold deposition, the hydrodynamic radius of the nanoparticles was changed from 23.2±2.2 nm to 31.7±2.3 nm, indicating an 8-nm thickness for the gold shell. The Fe@Au NPs were functionalized by lipoic acid (LA) and further conjugated with a polyarginine cell permeation peptide, NH2GR11. All the Fe@Au NPs stayed nearly 100% intact in either PBS or rat serum within 72 h. Cell labeling with the LA-modified Fe@Au NPs and NH2GR11-conjugated Fe@Au NPs was conducted by using a human prostate cancer cell line (PC-3). It was shown that NH2GR11 was able to increase the nanoparticle loading to PC-3 cells by 2–3 times. Shown in a pilot dual-modality imaging study, the LA-modified Fe@Au NP labeled cells could be visualized by both MRI and autoradiography imaging if the labeled PC-3 cell concentrations were above 1 × 105 cells/mL. The cell permeation peptide, NH2GR11, could significantly enhance the dual-modality detection sensitivity of the nanoplatform labeled PC-3 cells.