Single-nanometer iron oxide nanoparticles as tissue-permeable MRI contrast agents

Wei, He; Wiśniowska, Agata; Fan, Jingxuan; Harvey, Peter; Li, Yuanyuan; Wu, Victoria; Hansen, Eric C.; Zhang, Juanye; Kaul, Michael G.; Frey, Abigail M.; Adam, Gerhard; Frenkel, Anatoly I.; Bawendi, Moungi G.; Jasanoff, Alan

doi:10.1073/pnas.2102340118

Title: Single-nanometer iron oxide nanoparticles as tissue-permeable MRI contrast agents

Journal Article · Tue Oct 19 00:00:00 EDT 2021 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.2102340118· OSTI ID:1832767

Wei, He ^[1]; Wiśniowska, Agata ^[1]; Fan, Jingxuan ^[1]; Harvey, Peter ^[1]; Li, Yuanyuan ^[2]; Wu, Victoria ^[1]; Hansen, Eric C. ^[1]; Zhang, Juanye ^[1]; Kaul, Michael G. ^[3]; Frey, Abigail M. ^[1]; Adam, Gerhard ^[3];

^[4]; Bawendi, Moungi G. ^[1];

^[1]

Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
Stony Brook Univ., NY (United States)
University Medical Center Hamburg-Eppendorf (Germany)
Stony Brook Univ., NY (United States); Brookhaven National Lab. (BNL), Upton, NY (United States)

Magnetic nanoparticles are robust contrast agents for MRI and often produce particularly strong signal changes per particle. Leveraging these effects to probe cellular- and molecular-level phenomena in tissue can, however, be hindered by the large sizes of typical nanoparticle contrast agents. To address this limitation, we introduce single-nanometer iron oxide (SNIO) particles that exhibit superparamagnetic properties in conjunction with hydrodynamic diameters comparable to small, highly diffusible imaging agents. These particles efficiently brighten the signal in T ₁-weighted MRI, producing per-molecule longitudinal relaxation enhancements over 10 times greater than conventional gadolinium-based contrast agents. We show that SNIOs permeate biological tissue effectively following injection into brain parenchyma or cerebrospinal fluid. We also demonstrate that SNIOs readily enter the brain following ultrasound-induced blood–brain barrier disruption, emulating the performance of a gadolinium agent and providing a basis for future biomedical applications. Finally, these results thus demonstrate a platform for MRI probe development that combines advantages of small-molecule imaging agents with the potency of nanoscale materials.

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Research Organization:: Brookhaven National Lab. (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); Massachusetts General Hospital; National Science Foundation (NSF); European Union (EU)

Grant/Contract Number:: SC0012704; SC0012335; DMR-0520547; 654000; R24 MH109081; UF1 NS107712; R01 DA038642; R90 DA023427; 105932/Z/14/Z; DMR-1911592

OSTI ID:: 1832767

Report Number(s):: BNL-222429-2021-JAAM

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 118, Issue 42; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

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