title: Surface modification-mediated biodistribution of ¹³C-fullerene C₆₀ in vivo.
abstract: 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
  (13)C skeleton-labeled fullerene C60 ((13)C-C60) was functionalized with carboxyl groups ((13)C-C60-COOH) or hydroxyl groups ((13)C-C60-OH). Male ICR mice (~25 g) were exposed to a single dose of 400 μg of (13)C-C60-COOH or (13)C-C60-OH in 200 μL 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 C60-COOH and C60-OH after their intravenous injection, whereas unmodified C60 was mainly found in the liver, spleen and lung. The total uptakes in liver and spleen followed the order: C60 > > C60-COOH > C60-OH. The distribution rate over 24 h followed the order: C60 > C60-OH > C60-COOH. C60-COOH and C60-OH were both cleared from the body at 7 d post exposure. C60-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 C60-OH was more widespread than that of C60-COOH after intraperitoneal injection.
  
  
  CONCLUSIONS
  The surface modification of fullerene C60 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 C60 and improve its biocompatibility, which would be beneficial for biomedical applications.
authors.affiliation: Northwest University, Xi'an, 710069, P. R. China. wangchl@ihep.ac.cn.|CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, P. R. China. wangchl@ihep.ac.cn.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Chemistry and Environment Protection Engineering, Southwest University for Nationalities, Chengdu, 610041, P. R. China. 1023699356@qq.com.
authors.forename: Yitong
authors.initials: Y
authors.lastname: Bai
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, P. R. China. lihl@ihep.ac.cn.|College of Chemistry and Environment Protection Engineering, Southwest University for Nationalities, Chengdu, 610041, P. R. China. lihl@ihep.ac.cn.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Chemistry and Environment Protection Engineering, Southwest University for Nationalities, Chengdu, 610041, P. R. China. 326369551@qq.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Liao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, P. R. China. lijx@ihep.ac.cn.|Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, P.R. China. lijx@ihep.ac.cn.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, P.R. China. hanzhang@iue.ac.cn.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, P.R. China. xzhang@iue.ac.cn.
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Northwest University, Xi'an, 710069, P. R. China. sjzhang1998@163.com.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, P. R. China. yangst@pku.edu.cn.|College of Chemistry and Environment Protection Engineering, Southwest University for Nationalities, Chengdu, 610041, P. R. China. yangst@pku.edu.cn.
authors.forename: Sheng-Tao
authors.initials: ST
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, P. R. China. changxl@ihep.ac.cn.
authors.forename: Xue-Ling
authors.initials: XL
authors.lastname: Chang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002247:Carbon Isotopes; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D037741:Fullerenes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006900:Hydroxylation; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D008813:Mice, Inbred ICR; D018482:Muscle, Skeletal / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D002247:Carbon Isotopes; D002264:Carboxylic Acids; D037741:Fullerenes; C069837:fullerene C60