Memorial Sloan-Kettering Cancer System,
Keywords: carbon nanotube, fibrillar pharmacology, liver, receptor-mediated
Summary:Fibrillar nanocarbon has been investigated as a potential component for designing drug delivery platforms. Accretion and clearance from critical tissues directly correlate with the chemical and physical modifications of this nanomaterial. The liver accumulates most particulate drugs to some degree and is therefore of critical importance in regard to understanding the hepatic pharmacology and toxicity of carbon nanotubes. This water-soluble nanomaterial localized in the liver sinusoids in a process mediated by specialized scavenger receptors. Herein, a complete description of hepatic cytodistribution, receptor-mediated endocytosis, cellular trafficking, and toxicity of covalently functionalized single walled carbon nanotubes will be presented. A mechanism for hepatobiliary elimination will also be proposed. This unexpected cytodistribution profile and biliary mode of clearance, in conjunction with the rapid renal elimination via glomerular filtration that we showed previously, suggests that drug-based applications of fibrillar nanocarbon will be feasible in humans.