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

  • He Wei (Shared first author)
  • Agata Wiśniowska (Shared first author)
  • 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 (Shared last author)
  • Alan Jasanoff (Shared last author)

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 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.

Bibliographical data

Original languageEnglish
Article numbere2102340118
ISSN0027-8424
DOIs
Publication statusPublished - 19.10.2021
PubMed 34654743