Dual-modality NIRF-MRI cubosomes and hexosomes: High throughput formulation and in vivo biodistribution

Engineered nanoparticles with multiple complementary imaging modalities are of great benefit to the rapidtreatment and diagnosis of disease in various organs. Herein, we report the formulation of cubosomes andhexosomes that carry multiple amphiphilic imaging contrast agents in their self-assembled lipid bilayers. Thisis the first report of the use of both near infrared fluorescent (NIRF) imaging and gadolinium lipid based magneticresonance (MR) imaging modalities in cubosomes and hexosomes. High-throughput screening was used to rapidlyoptimize formulations with desirable nano-architectures and low in vitro cytotoxicity. The dual-modal imagingnanoparticles in vivo biodistribution and organ specific contrast enhancement were then studied. The NIRF invivo imaging results indicated accumulation of both cubosomes and hexosomes in the liver and spleen of mice upto 20 h post-injection. Remarkably, the biodistribution of the nanoparticle formulations was affected by themesophase (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 enhancedcontrast in the liver and spleen