@article{9b34e9673b9241aea9f57ed3b99a24ff,
title = "Maximizing Magnetic Resonance Contrast in Gd(III) Nanoconjugates: Investigation of Proton Relaxation in Zirconium Metal-Organic Frameworks",
abstract = "Gadolinium(III) nanoconjugate contrast agents (CAs) provide significant advantages over small-molecule complexes for magnetic resonance imaging (MRI), namely increased Gd(III) payload and enhanced proton relaxation efficiency (relaxivity, r1). Previous research has demonstrated that both the structure and surface chemistry of the nanomaterial substantially influence contrast. We hypothesized that inserting Gd(III) complexes in the pores of a metal-organic framework (MOF) might offer a unique strategy to further explore the parameters of nanomaterial structure and composition, which influence relaxivity. Herein, we postsynthetically incorporate Gd(III) complexes into Zr-MOFs using solvent-assisted ligand incorporation (SALI). Through the study of Zr-based MOFs, NU-1000 (nano and micronsize particles) and NU-901, we investigated the impact of particle size and pore shape on proton relaxivity. The SALI-functionalized Gd nano NU-1000 hybrid material displayed the highest loading of the Gd(III) complex (1.9 ± 0.1 complexes per node) and exhibited the most enhanced proton relaxivity (r1 of 26 ± 1 mM-1 s-1 at 1.4 T). Based on nuclear magnetic relaxation dispersion (NMRD) analysis, we can attribute the performance of Gd nano NU-1000 to the nanoscale size of the MOF particles and larger pore size that allows for rapid water exchange. We have demonstrated that SALI is a promising method for incorporating Gd(III) complexes into MOF materials and identified crucial design parameters for the preparation of next generation Gd(III)-functionalized MOF MRI contrast agents. ",
keywords = "contrast agent, gadolinium, magnetic resonance, metal-organic frameworks, relaxivity",
author = "McLeod, {Shaunna M.} and Lee Robison and Giacomo Parigi and Alyssa Olszewski and Drout, {Riki J.} and Xinyi Gong and Timur Islamoglu and Claudio Luchinat and Farha, {Omar K.} and Meade, {Thomas J.}",
note = "Funding Information: S.M.M. gratefully acknowledges the NSF Graduate Research Fellowship Grant no. DGE-1842165. L.R.{\textquoteright}s contribution to this work is based on work supported by the U.S. Department of Energy (DOE), Office of Science, Office of Workforce Development for Teachers and Scientists, and Office of Science Graduate Student Research (SCGSR) program. The SCGSR program is administered by the Oak Ridge Institute for Science and Education (ORISE) for the DOE. ORISE is managed by ORAU under contract DE-SC0014664. R.J.D. appreciates the support of the Northwestern University Ryan Fellowship granted by the International Institute of Nanotechnology and The Graduate School at Northwestern University. G.P. and C.L. acknowledge the support from the Fondazione Cassa di Risparmio di Firenze, the MIUR PRIN 2017A2KEPL, and Instruct-ERIC, an ESFRI Landmark, supported by national member subscriptions. Specifically, we thank the Instruct-ERIC Core Centre CERM, Italy. The COST Action CA15209 (EURELAX) is also acknowledged. O.K.F. gratefully acknowledges the financial support from the Air Force Research Laboratory (FA8650–15–2–5518). T.J.M. gratefully acknowledges the support from the NIH National Institute of Biomedical Imaging and Bioengineering award no. R01EB005866–6. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Use was made of the IMSERC X-ray facility at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205), the State of Illinois, and the International Institute for Nanotechnology (IIN). This work made use of the EPIC facility of Northwestern University{\textquoteright}s NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1720139) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, though the IIN. Imaging work (7 T relaxivity) was performed by E. Waters at the Northwestern University Center for Advanced Molecular Imaging generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. Elemental analysis was performed at the Northwestern University Quantitative Bio-element Imaging Center generously supported by NASA Ames Research Center Grant NNA04CC36G. Publisher Copyright: Copyright {\textcopyright} 2020 American Chemical Society.",
year = "2020",
month = sep,
day = "16",
doi = "10.1021/acsami.0c13571",
language = "English (US)",
volume = "12",
pages = "41157--41166",
journal = "ACS Applied Materials and Interfaces",
issn = "1944-8244",
publisher = "American Chemical Society",
number = "37",
}