High relaxivity Gd(III)-DNA gold nanostars: investigation of shape effects on proton relaxation.
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 (r1), 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 r1 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.
Matthew W
MW
Rotz
Kayla S B
KS
Culver
∥Magnetic Resonance Center (CERM) and Department of Chemistry, University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Italy.
Giacomo
G
Parigi
Keith W
KW
MacRenaris
∥Magnetic Resonance Center (CERM) and Department of Chemistry, University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Italy.
Claudio
C
Luchinat
Teri W
TW
Odom
Thomas J
TJ
Meade
D001692:Biological Transport; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008422:Materials Testing; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D011522:Protons
D003287:Contrast Media; D011522:Protons; D006046:Gold; D004247:DNA; D005682:Gadolinium
contrast agent; gadolinium; magnetic resonance; nanostar; nuclear magnetic resonance dispersion; relaxivity; second-sphere