Preparation and evaluation of a radioisotope-incorporated iron oxide core/Au shell nanoplatform for dual modality imaging

Magnetic gold-coated iron oxide nanoparticles (FeΑu 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 FeΑu 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 FeΑu NPs were functionalized by lipoic acid (LA) and further conjugated with a polyarginine cell permeation peptide, NH₂GR11. All the FeΑu NPs stayed nearly 100% intact in either PBS or rat serum within 72 h. Cell labeling with the LA-modified FeΑu NPs and NH₂GR11-conjugated FeΑu 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 FeΑu 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.