title: Dual-modality NIRF-MRI cubosomes and hexosomes: High throughput formulation and in vivo biodistribution.
abstract: Engineered nanoparticles with multiple complementary imaging modalities are of great benefit to the rapid treatment and diagnosis of disease in various organs. Herein, we report the formulation of cubosomes and hexosomes that carry multiple amphiphilic imaging contrast agents in their self-assembled lipid bilayers. This is the first report of the use of both near infrared fluorescent (NIRF) imaging and gadolinium lipid based magnetic resonance (MR) imaging modalities in cubosomes and hexosomes. High-throughput screening was used to rapidly optimize formulations with desirable nano-architectures and low in vitro cytotoxicity. The dual-modal imaging nanoparticles in vivo biodistribution and organ specific contrast enhancement were then studied. The NIRF in vivo imaging results indicated accumulation of both cubosomes and hexosomes in the liver and spleen of mice up to 20h post-injection. Remarkably, the biodistribution of the nanoparticle formulations was affected by the mesophase (i.e. cubic or hexagonal), a finding of significant importance for the future use of these compounds, with hexosomes showing higher accumulation in the spleen than the liver compared to cubosomes. Furthermore, in vivo MRI data of animals injected with either type of lyotropic liquid crystal nanoparticle displayed enhanced contrast in the liver and spleen.
authors.affiliation: CSIRO Manufacturing, Clayton, Victoria 3168, Australia; Australian Synchrotron, Clayton, Victoria 3168, Australia; RMIT University, Melbourne, Victoria 3000, Australia. Electronic address: nhiem.tran@rmit.edu.au.
authors.forename: Nhiem
authors.initials: N
authors.lastname: Tran
authors.affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bye
authors.affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Moffat
authors.affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria 3010, Australia; The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052, Australia.
authors.forename: David K
authors.initials: DK
authors.lastname: Wright
authors.affiliation: Myeloma Research Group, Australian Centre for Blood Diseases, Monash Central Clinical School, The Alfred Hospital, Melbourne, Victoria 3004, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Cuddihy
authors.affiliation: CSIRO Australian Animal Health Laboratory, East Geelong, Victoria 3219, Australia.
authors.forename: Tracey M
authors.initials: TM
authors.lastname: Hinton
authors.affiliation: Australian Synchrotron, Clayton, Victoria 3168, Australia.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Hawley
authors.affiliation: CSIRO Manufacturing, Clayton, Victoria 3168, Australia; ARC Training Centre for Biodevices, Faculty of Science Engineering and Technology, Swinburne University of Technology, Melbourne, Victoria 3122, Australia.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Reynolds
authors.affiliation: CSIRO Manufacturing, Clayton, Victoria 3168, Australia.
authors.forename: Lynne J
authors.initials: LJ
authors.lastname: Waddington
authors.affiliation: CSIRO Manufacturing, Clayton, Victoria 3168, Australia.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mulet
authors.affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Turnley
authors.affiliation: Australian New Zealand Intensive Care Research Centre, Monash University, Victoria 3800, Australia; Department of Child Health, Barrow Neurological Institute, University of Arizona, Phoenix, AZ 85004, USA.
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Morganti-Kossmann
authors.affiliation: CSIRO Manufacturing, Clayton, Victoria 3168, Australia. Electronic address: ben.muir@csiro.au.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Muir
mesh_terms: D000818:Animals; D016466:CHO Cells; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003412:Cricetulus; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D061848:Optical Imaging; D020298:U937 Cells
chemical_list: D003287:Contrast Media
keywords: Biodistribution; Cubosome; Hexosome; Imaging; Lipid; MRI; Multifunctional; Nanoparticles