Molecular imaging of activated platelets via antibody-targeted ultra-small iron oxide nanoparticles displaying unique dual MRI contrast

Hang T Ta, Zhen Li, Christoph E. Hagemeyer, Gary Cowin, Shaohua Zhang, Jathushan Palasubramaniam, Karen Alt, Xiaowei Wang, Karlheinz Peter, Andrew Keith Whittaker

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Magnetic resonance imaging (MRI) is a powerful and indispensable tool in medical research, clinical diagnosis, and patient care due to its high spatial resolution and non-limited penetration depth. The simultaneous use of positive and negative MRI imaging that employs the same contrast agents will significantly improve detection accuracy. Here we report the development of functional multimodal iron oxide nanoparticles for targeted MRI of atherothrombosis using a combination of chemical and biological conjugation techniques. Monodisperse, water-soluble and biocompatible ultra-small magnetic dual contrast iron oxide nanoparticles (DCIONs) were generated using a high-temperature co-precipitation route and appeared to be efficient positive and negative dual contrast agents for magnetic resonance imaging. Using a unique chemo-enzymatic approach involving copper-free click chemistry and Staphylococcus aureus sortase A enzyme conjugation, DCIONs were functionalized with single-chain antibodies (scFv) directed against activated platelets for targeting purposes. The DCIONs were also labelled with fluorescent molecules to allow for optical imaging. The antigen binding activity of the scFv was retained and resulted in the successful targeting of contrast agents to thrombosis as demonstrated in a range of in vitro and in vivo experiments. T1- and T2-weighted MRI of thrombi was recorded and demonstrated the great potential of dual T1/T2 contrast iron oxide particles in imaging of cardiovascular disease.

Original languageEnglish
Pages (from-to)31-42
Number of pages12
JournalBiomaterials
Volume134
DOIs
Publication statusPublished - 1 Jul 2017

Keywords

  • Cardiovascular disease
  • Dual contrast iron oxide nanoparticle
  • Magnetic resonance imaging
  • Molecular imaging
  • Platelet
  • Sortase

Cite this

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title = "Molecular imaging of activated platelets via antibody-targeted ultra-small iron oxide nanoparticles displaying unique dual MRI contrast",
abstract = "Magnetic resonance imaging (MRI) is a powerful and indispensable tool in medical research, clinical diagnosis, and patient care due to its high spatial resolution and non-limited penetration depth. The simultaneous use of positive and negative MRI imaging that employs the same contrast agents will significantly improve detection accuracy. Here we report the development of functional multimodal iron oxide nanoparticles for targeted MRI of atherothrombosis using a combination of chemical and biological conjugation techniques. Monodisperse, water-soluble and biocompatible ultra-small magnetic dual contrast iron oxide nanoparticles (DCIONs) were generated using a high-temperature co-precipitation route and appeared to be efficient positive and negative dual contrast agents for magnetic resonance imaging. Using a unique chemo-enzymatic approach involving copper-free click chemistry and Staphylococcus aureus sortase A enzyme conjugation, DCIONs were functionalized with single-chain antibodies (scFv) directed against activated platelets for targeting purposes. The DCIONs were also labelled with fluorescent molecules to allow for optical imaging. The antigen binding activity of the scFv was retained and resulted in the successful targeting of contrast agents to thrombosis as demonstrated in a range of in vitro and in vivo experiments. T1- and T2-weighted MRI of thrombi was recorded and demonstrated the great potential of dual T1/T2 contrast iron oxide particles in imaging of cardiovascular disease.",
keywords = "Cardiovascular disease, Dual contrast iron oxide nanoparticle, Magnetic resonance imaging, Molecular imaging, Platelet, Sortase",
author = "Ta, {Hang T} and Zhen Li and Hagemeyer, {Christoph E.} and Gary Cowin and Shaohua Zhang and Jathushan Palasubramaniam and Karen Alt and Xiaowei Wang and Karlheinz Peter and Whittaker, {Andrew Keith}",
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Molecular imaging of activated platelets via antibody-targeted ultra-small iron oxide nanoparticles displaying unique dual MRI contrast. / Ta, Hang T; Li, Zhen; Hagemeyer, Christoph E.; Cowin, Gary; Zhang, Shaohua; Palasubramaniam, Jathushan; Alt, Karen; Wang, Xiaowei; Peter, Karlheinz; Whittaker, Andrew Keith.

In: Biomaterials, Vol. 134, 01.07.2017, p. 31-42.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Molecular imaging of activated platelets via antibody-targeted ultra-small iron oxide nanoparticles displaying unique dual MRI contrast

AU - Ta, Hang T

AU - Li, Zhen

AU - Hagemeyer, Christoph E.

AU - Cowin, Gary

AU - Zhang, Shaohua

AU - Palasubramaniam, Jathushan

AU - Alt, Karen

AU - Wang, Xiaowei

AU - Peter, Karlheinz

AU - Whittaker, Andrew Keith

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