Gd(III)-Gold Nanoconjugates Provide Remarkable Cell Labeling for High Field Magnetic Resonance Imaging

In vivo cell tracking is vital for understanding migrating cell populations, particularly cancer and immune cells. Magnetic resonance (MR) imaging for long-term tracking of transplanted cells in live organisms requires cells to effectively internalize Gd(III) contrast agents (CAs). Clinical Gd(III)-based CAs require high dosing concentrations and extended incubation times for cellular internalization. To combat this, we have devised a series of Gd(III)-gold nanoconjugates (Gd@AuNPs) with varied chelate structure and nanoparticle-chelate linker length, with the goal of labeling and imaging breast cancer cells. These new Gd@AuNPs demonstrate significantly enhanced labeling compared to previous Gd(III)-gold-DNA nanoconstructs. Variations in Gd(III) loading, surface packing, and cell uptake were observed among four different Gd@AuNP formulations suggesting that linker length and surface charge play an important role in cell labeling. The best performing Gd@AuNPs afforded 23.6 ± 3.6 fmol of Gd(III) per cell at an incubation concentration of 27.5 μM-this efficiency of Gd(III) payload delivery (Gd(III)/cell normalized to dose) exceeds that of previous Gd(III)-Au conjugates and most other Gd(III)-nanoparticle formulations. Further, Gd@AuNPs were well-tolerated in vivo in terms of biodistribution and clearance, and supports future cell tracking applications in whole-animal models.