Metal-free and MRI visible theranostic lyotropic liquid crystal nitroxide-based nanoparticles.
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 Omniscan™ 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.
CSIRO Materials Science and Engineering, Bayview Avenue, Clayton 3168, Australia. ben.muir@csiro.au
Benjamin W
BW
Muir
Durga P
DP
Acharya
Danielle F
DF
Kennedy
Xavier
X
Mulet
Richard A
RA
Evans
Suzanne M
SM
Pereira
Kim L
KL
Wark
Ben J
BJ
Boyd
Tri-Hung
TH
Nguyen
Tracey M
TM
Hinton
Lynne J
LJ
Waddington
Nigel
N
Kirby
David K
DK
Wright
Hong X
HX
Wang
Gary F
GF
Egan
Bradford A
BA
Moffat
D000818:Animals; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D020285:Cryoelectron Microscopy; D005233:Fatty Alcohols / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D057809:HEK293 Cells; D006801:Humans; D050866:Liquid Crystals / Q000737:chemistry* / Q000633:toxicity; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008670:Metals / Q000737:chemistry*; D053758:Nanoparticles / Q000633:toxicity / Q000648:ultrastructure; D009589:Nitrogen Oxides / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D053838:Scattering, Small Angle; D017356:Synchrotrons; D014961:X-Ray Diffraction
D005233:Fatty Alcohols; D008670:Metals; D009589:Nitrogen Oxides; C508873:3,7,11,15-tetramethyl-1,2,3-hexadecanetriol; C039900:nitroxyl