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

TY - JOUR

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

AU - Wei, He

AU - Wiśniowska, 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

PY - 2021/10/19

Y1 - 2021/10/19

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

KW - Animals

KW - Blood-Brain Barrier

KW - Contrast Media/administration & dosage

KW - Magnetic Iron Oxide Nanoparticles/administration & dosage

KW - Magnetic Resonance Imaging/methods

KW - Particle Size

KW - Permeability

KW - Rats

U2 - 10.1073/pnas.2102340118

DO - 10.1073/pnas.2102340118

M3 - SCORING: Journal article

C2 - 34654743

VL - 118

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 42

M1 - e2102340118

ER -