Metal-free and MRI visible theranostic lyotropic liquid crystal nitroxide-based nanoparticles

Benjamin W Muir, Durga P Acharya, Danielle Kennedy, Xavier Mulet, Richard Alexander Evans, Suzanne M Periera, Kim Wark, Benjamin James Boyd, Tri-Hung Nguyen, Tracey M Hinton, Lynne Waddington, Nigel Kirby, David K Wright, Hong Xin Wang, Gary F Egan, Braford A Moffat

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61 Citations (Scopus)

Abstract

The development of improved, low toxicity, clinically viable nanomaterials that provide MRI contrast have tremendous potential to form the basis of translatable theranostic agents. Herein we describe a class of MRI visible materials based on lyotropic liquid crystal nanoparticles loaded with a paramagnetic nitroxide lipid. These readily synthesized nanoparticles achieved enhanced proton-relaxivities on the order of clinically used gadolinium complexes such as Omniscana?? without the use of heavy metal coordination complexes. Their low toxicity, high water solubility and colloidal stability in buffer resulted in them being well tolerated in vitro and in vivo. The nanoparticles were initially screened in vitro for cytotoxicity and subsequently a defined concentration range was tested in rats to determine the maximum tolerated dose. Pharmacokinetic profiles of the candidate nanoparticles were established in vivo on IV administration to rats. The lyotropic liquid crystal nanoparticles were proven to be effective liver MRI contrast agents. We have demonstrated the effective in vivo performance of a T1 enhancing, biocompatible, colloidally stable, amphiphilic MRI contrast agent that does not contain a metal.
Original languageEnglish
Pages (from-to)2723 - 2733
Number of pages11
JournalBiomaterials
Volume33
Issue number9
DOIs
Publication statusPublished - 2012

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