Surface modification-mediated biodistribution of 13C-fullerene C60 in vivo

Background: Functionalization is believed to have a considerable impact on the biodistribution of fullerene in vivo. However, a direct comparison of differently functionalized fullerenes is required to prove the hypothesis. The purpose of this study was to investigate the influences of surface modification on the biodistribution of fullerene following its exposure via several routs of administration. Methods: C-13 skeleton-labeled fullerene C-60 (C-13-C-60) was functionalized with carboxyl groups (C-13-C-60-COOH) or hydroxyl groups (C-13-C-60-OH). Male ICR mice (similar to 25 g) were exposed to a single dose of 400 mu g of C-13-C-60-COOH or C-13-C-60-OH in 200 mu L of aqueous 0.9% NaCl solution by three different exposure pathways, including tail vein injection, gavage and intraperitoneal exposure. Tissue samples, including blood, heart, liver, spleen, stomach, kidneys, lungs, brain, large intestine, small intestine, muscle, bone and skin were subsequently collected, dissected, homogenized, lyophilized, and analyzed by isotope ratio mass spectrometry. Results: The liver, bone, muscle and skin were found to be the major target organs for C-60-COOH and C-60-OH after their intravenous injection, whereas unmodified C-60 was mainly found in the liver, spleen and lung. The total uptakes in liver and spleen followed the order: C-60 >> C-60-COOH > C-60-OH. The distribution rate over 24 h followed the order: C-60 > C-60-OH > C-60-COOH. C-60-COOH and C-60-OH were both cleared from the body at 7 d post exposure. C-60-COOH was absorbed in the gastrointestinal tract following gavage exposure and distributed into the heart, liver, spleen, stomach, lungs, intestine and bone tissues. The translocation of C-60-OH was more widespread than that of C-60-COOH after intraperitoneal injection. Conclusions: The surface modification of fullerene C-60 led to a decreased in its accumulation level and distribution rate, as well as altering its target organs. These results therefore demonstrate that the chemical functionalization of fullerene had a significant impact on its translocation and biodistribution properties. Further surface modifications could therefore be used to reduce the toxicity of C-60 and improve its biocompatibility, which would be beneficial for biomedical applications.