High Relaxivity Gd(III)–DNA Gold Nanostars: Investigation of Shape Effects on Proton Relaxation

• Published in: ACS nano 2015-03, Vol.9 (3), p.3385-3396
• Main Authors: Rotz, Matthew W, Culver, Kayla S. B, Parigi, Giacomo, MacRenaris, Keith W, Luchinat, Claudio, Odom, Teri W, Meade, Thomas J
• Format: Article
• Language: English
• Subjects: Biological Transport; Cell Line, Tumor; Conjugation; Contrast agents; Contrast Media - chemistry; Contrast Media - metabolism; Contrast Media - pharmacology; Dispersions; DNA - chemistry; Gadolinium - chemistry; Gold; Gold - chemistry; Humans; Magnetic resonance; Magnetic Resonance Imaging; Materials Testing; Models, Molecular; Nanostructure; Nanostructures - chemistry; Nucleic Acid Conformation; Particle shape; Protons
• ISSN: 1936-0851; 1936-086X; 1936-086X
• DOI: 10.1021/nn5070953

Gadolinium(III) nanoconjugate contrast agents (CAs) have distinct advantages over their small-molecule counterparts in magnetic resonance imaging. In addition to increased Gd(III) payload, a significant improvement in proton relaxation efficiency, or relaxivity (r 1), is often observed. In this work, we describe the synthesis and characterization of a nanoconjugate CA created by covalent attachment of Gd(III) to thiolated DNA (Gd(III)–DNA), followed by surface conjugation onto gold nanostars (DNA–Gd@stars). These conjugates exhibit remarkable r 1 with values up to 98 mM–1 s–1. Additionally, DNA–Gd@stars show efficient Gd(III) delivery and biocompatibility in vitro and generate significant contrast enhancement when imaged at 7 T. Using nuclear magnetic relaxation dispersion analysis, we attribute the high performance of the DNA–Gd@stars to an increased contribution of second-sphere relaxivity compared to that of spherical CA equivalents (DNA–Gd@spheres). Importantly, the surface of the gold nanostar contains Gd(III)–DNA in regions of positive, negative, and neutral curvature. We hypothesize that the proton relaxation enhancement observed results from the presence of a unique hydrophilic environment produced by Gd(III)–DNA in these regions, which allows second-sphere water molecules to remain adjacent to Gd(III) ions for up to 10 times longer than diffusion. These results establish that particle shape and second-sphere relaxivity are important considerations in the design of Gd(III) nanoconjugate CAs.