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

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

doi:10.1073/pnas.2102340118

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

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

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

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 T₁-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. These results thus demonstrate a platform for MRI probe development that combines advantages of small-molecule imaging agents with the potency of nanoscale materials.

Original language	English
Article number	e2102340118
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	118
Issue number	42
DOIs	https://doi.org/10.1073/pnas.2102340118
State	Published - Oct 19 2021
Externally published	Yes

Funding

A.W. was funded by the Advanced Multimodal Neuroimaging Training Program at the Massachusetts General Hospital through NIH Grant R90 DA023427. Y.L. and A.I.F. acknowledge support from NSF Grant DMR-1911592. A.M.F. was funded by the C. Michael Mohr Scholarship as awarded by the MIT Department of Chemical Engineering. This project was funded by an MIT Deshpande Center Innovation Grant (to M.G.B.) and NIH Grants R24 MH109081 (to A.J.), UF1 NS107712 (to A.J.), and R01 DA038642 (to A.J.). This work also benefited from the use of the SasView application, originally developed under NSF Award DMR-0520547. SasView contains code developed with funding from the European Union's Horizon 2020 Research and Innovation Programme under Science and Innovation with Neutrons in Europe 2020 (SINE2020) Project Grant 654000. This research used beamline 7-BM (Quick X-ray Absorption and Scattering, QAS) of the National Synchrotron Light Source II, a Department of Energy (DOE) Office of Science User Facility operated by Brookhaven National Laboratory under Contract DE-SC0012704. Beam-line operations were supported in part by the Synchrotron Catalysis Consortium (DOE Office of Basic Energy Sciences Grant DE-SC0012335). We thank Oliver Bruns for helpful discussions, Yong Zhang and Patrick Boisvert for help with TEM and SQUID magnetometry, Jiahao Huang for help with X-ray absorption fine structure measurements, and Athena Ortega and Francisco Acosta for assistance with MATLAB scripts. ACKNOWLEDGMENTS. A.W. was funded by the Advanced Multimodal Neuroimaging Training Program at the Massachusetts General Hospital through NIH Grant R90 DA023427. Y.L. and A.I.F. acknowledge support from NSF Grant DMR-1911592. A.M.F. was funded by the C. Michael Mohr Scholarship as awarded by the MIT Department of Chemical Engineering. This project was funded by an MIT Deshpande Center Innovation Grant (to M.G.B.) and NIH Grants R24 MH109081 (to A.J.), UF1 NS107712 (to A.J.), and R01 DA038642 (to A.J.). This work also benefited from the use of the SasView application, originally developed under NSF Award DMR-0520547. SasView contains code developed with funding from the European Union’s Horizon 2020 Research and Innovation Programme under Science and Innovation with Neutrons in Europe 2020 (SINE2020) Project Grant 654000. This research used beamline 7-BM (Quick X-ray Absorption and Scattering, QAS) of the National Synchrotron Light Source II, a Department of Energy (DOE) Office of Science User Facility operated by Brookhaven National Laboratory under Contract DE-SC0012704. Beam-line operations were supported in part by the Synchrotron Catalysis Consortium (DOE Office of Basic Energy Sciences Grant DE-SC0012335). We thank Oliver Bruns for helpful discussions, Yong Zhang and Patrick Bois-vert for help with TEM and SQUID magnetometry, Jiahao Huang for help with X-ray absorption fine structure measurements, and Athena Ortega and Francisco Acosta for assistance with MATLAB scripts.

Keywords

Brain
Iron oxide nanoparticle
Magnetic resonance imaging
Molecular imaging

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10.1073/pnas.2102340118

Cite this

Wei, H., Wisniowska, A., Fan, J., Harvey, P., Li, Y., Wu, V., Hansen, E. C., Zhang, J., Kaul, M. G., Frey, A. M., Adam, G., Frenkel, A. I., Bawendi, M. G., & Jasanoff, A. (2021). Single-nanometer iron oxide nanoparticles as tissue-permeable MRI contrast agents. Proceedings of the National Academy of Sciences of the United States of America, 118(42), Article e2102340118. https://doi.org/10.1073/pnas.2102340118

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abstract = "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 T1-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. 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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Wei, H, Wisniowska, A, Fan, J, Harvey, P, Li, Y, Wu, V, Hansen, EC, Zhang, J, Kaul, MG, Frey, AM, Adam, G, Frenkel, AI, Bawendi, MG & Jasanoff, A 2021, 'Single-nanometer iron oxide nanoparticles as tissue-permeable MRI contrast agents', Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 42, e2102340118. https://doi.org/10.1073/pnas.2102340118

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AU - Wisniowska, Agata

AU - Fan, Jingxuan

AU - Harvey, Peter

AU - Li, Yuanyuan

AU - Wu, Victoria

AU - Hansen, Eric C.

AU - Zhang, Juanye

AU - Kaul, Michael G.

AU - Frey, Abigail M.

AU - Adam, Gerhard

AU - Frenkel, Anatoly I.

AU - Bawendi, Moungi G.

AU - Jasanoff, Alan

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N2 - 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 T1-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. These results thus demonstrate a platform for MRI probe development that combines advantages of small-molecule imaging agents with the potency of nanoscale materials.

AB - 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 T1-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. 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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Single-nanometer iron oxide nanoparticles as tissue-permeable MRI contrast agents

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