Deconvoluting hepatic processing of carbon nanotubes.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Drug Delivery

Background:

• Single-wall carbon nanotubes offer potential for drug delivery but face clinical translation challenges.
• Mechanisms of nanotube accumulation and clearance in organs remain unclear.
• The liver's complex cellular environment impacts particulate drug disposition.

Purpose of the Study:

• To elucidate the hepatic processing of covalently functionalized single-wall carbon nanotubes.
• To investigate the cellular mechanisms of nanotube uptake and elimination in the liver.
• To assess the in vivo behavior and biocompatibility of nanotubes for potential clinical use.

Main Methods:

• Investigated ammonium-functionalized carbon nanotubes in a murine liver model.
• Utilized receptor-mediated endocytosis and cellular trafficking studies.
• Evaluated nanotube pharmacokinetics and biocompatibility in non-human primates (cynomolgus monkeys).

Main Results:

• Nanotubes preferentially localized in liver sinusoidal endothelium, not macrophages.
• Stabilin receptors were identified as mediating nanotube endocytic clearance.
• No observed cell death or immune cell infiltration indicated biocompatibility.
• Pharmacologic profiles in non-human primates mirrored murine data.

Conclusions:

• Hepatic processing involves receptor-mediated endocytosis and biliary elimination.
• Stabilin receptor-mediated clearance and liver localization are key.
• Nanotubes demonstrate biocompatibility and predictable pharmacologic behavior across species, supporting clinical translation.