Dermatomed porcine skin was fixed to a flexing device and topically dosed with 33.5 mg.mL-1 of an aqueous solution of a fullerene-substituted phenylalanine (Baa) derivative of a nuclear localization peptide sequence (Baa-Lys(FITC)-NLS). Skin was flexed for 60 or 90 min or left unflexed (control). Confocal microscopy depicted dermal penetration of the nanoparticles at 8 h in skin flexed for 60 and 90 min, whereas Baa-Lys(FITC)-NLS did not penetrate into the dermis of unflexed skin until 24 h. TEM analysis revealed fullerene-peptide localization within the intercellular spaces of the stratum granulosum.

Graphene and its derivatives (for example, nanoscale graphene oxide (NGO)) have emerged as extremely attractive nanomaterials for a wide range of applications, including diagnostics and therapeutics. In this work, we present a systematic study on the in vivo distribution and pulmonary toxicity of NGO for up to 3 months after exposure. Radioisotope tracing and morphological observation demonstrated that intratracheally instilled NGO was mainly retained in the lung. NGO could result in acute lung injury (ALI) and chronic pulmonary fibrosis. Such NGO-induced ALI was related to oxidative stress and could effectively be relieved with dexamethasone treatment. In addition, we found that the biodistribution of 125 I-NGO varied greatly from that of 125 I ions, hence it is possible that nanoparticulates could deliver radioactive isotopes deep into the lung, which might settle in numerous 'hot spots' that could result in mutations and cancers, raising environmental concerns about the large-scale production of graphene oxide. Keywords: biodistribution; graphene oxide; intratracheal instillation; mice; pulmonary toxicity INTRODUCTION Graphene is a recently discovered, two-dimensional nanomaterial with a one-atom thickness. 1 Graphene and its derivatives (for example, nanoscale graphene oxide (NGO)) have shown unique thermal, mechanical and electronic properties that have attracted tremendous attention in applications including nanocomposites and transistors, as well as diagnostics and therapeutics. [2][3][4] In particular, water-dispersible NGO has proven to be a promising nanocarrier for drug delivery. Hence, it is critically important to address the safety issue of NGO before its in vivo biomedical application.The lung is the primary organ invaded by nanomaterials because of the communication of this organ with the outside atmosphere through the respiratory tract. In addition, nanoparticles (o100 nm) have previously been found to deposit mainly in the lungs. 5 Therefore, intratracheal instillation was used to investigate the biodistribution and pulmonary toxicity of NGO in C57BL/6 mice for up to 3 months. We employed radioisotope tracing and conventional evaluation system to study the in vivo absorption, distribution, metabolism, excretion and toxicity of NGO in mice. Our finding on the apparent discrepancy in biodistribution of 125 I-NGO with iodine-125 ions also raises potential concerns on the identification of target organs and critical effects upon nuclear radiation exposure.

The reaction product of boric acid and the polysaccharide guaran (the major component of guar gum) has been investigated by 11B NMR spectroscopy. By comparison with the 11B NMR of boric acid and phenylboronic acid complexes of 1,2-diols (HOCMe2CMe2OH, cis-C6H10(OH)2, trans-C6H10(OH)2, o-C6H4(OH)2), 1,3-diols (neol-H2), monosaccharides (L-fucose, mannose and galactose) and disaccharides (cellobiose and sucrose) it is found that the guaran polymer is cross-linked via a borate complex of two 1,2-diols both forming chelate 5-membered ring cycles ([B5(2)]), this contrasts with previous proposals. Based upon steric constraints we propose that preferential cross-linking the guaran polymer occurs via the 3,4-diols of the galactose side chain. The DeltaH and DeltaS for complexation of boric acid to cis- and trans-1,2-cyclohexanediol have been determined, from the temperature dependence of the appropriate equilibrium constants, and used in conjunction with ab initio calculations on model compounds, to understand prior conflicting proposals for guaran-boric acid interactions. 11B NMR derived pH dependent equilibrium constants and ab initio calculations have been used to understand the reasons for the inefficiency of boric acid to cross-link guaran (almost 2 borate ions per 3 monosaccharide repeat units are required for a viscous gel suitable as a fracturing fluid): the most reactive sites on the component saccharides (mannose and galactose) are precluded from reaction by the nature of the guar structure; the comparable acidity (pKa) of the remaining guaran alcohol substituents and the water solvent, results in a competition between cross-linking and borate formation; a significant fraction of the boric acid is ineffective in cross-linking guar due to the modest equilibrium (Keq). In contrast to prior work, we present evidence for the reaction of alcohols with boric acid, rather than the borate anion. Based upon the results obtained for phenylboronic acid, alternative cross-linking agents are proposed.