Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 3385-3396 |
| Number of pages | 12 |
| Journal | ACS Nano |
| Volume | 9 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 24 2015 |
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Keywords
- contrast agent
- gadolinium
- magnetic resonance
- nanostar
- nuclear magnetic resonance dispersion
- relaxivity
- second-sphere
ASJC Scopus subject areas
- Engineering(all)
- Materials Science(all)
- Physics and Astronomy(all)
Cite this
High relaxivity Gd(III)-DNA gold nanostars : Investigation of shape effects on proton relaxation. / Rotz, Matthew W.; Culver, Kayla S B; Parigi, Giacomo; Macrenaris, Keith W.; Luchinat, Claudio; Odom, Teri W; Meade, Thomas J.
In: ACS Nano, Vol. 9, No. 3, 24.03.2015, p. 3385-3396.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - High relaxivity Gd(III)-DNA gold nanostars
T2 - Investigation of shape effects on proton relaxation
AU - Rotz, Matthew W.
AU - Culver, Kayla S B
AU - Parigi, Giacomo
AU - Macrenaris, Keith W.
AU - Luchinat, Claudio
AU - Odom, Teri W
AU - Meade, Thomas J.
PY - 2015/3/24
Y1 - 2015/3/24
N2 - 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.
AB - 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.
KW - contrast agent
KW - gadolinium
KW - magnetic resonance
KW - nanostar
KW - nuclear magnetic resonance dispersion
KW - relaxivity
KW - second-sphere
UR - http://www.scopus.com/inward/record.url?scp=84925666594&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925666594&partnerID=8YFLogxK
U2 - 10.1021/nn5070953
DO - 10.1021/nn5070953
M3 - Article
C2 - 25723190
AN - SCOPUS:84925666594
VL - 9
SP - 3385
EP - 3396
JO - ACS Nano
JF - ACS Nano
SN - 1936-0851
IS - 3
ER -