No abstract

a b s t r a c tSuccessful application of gold nanoparticles (AuNPs) in biomedicine requires extensive safety assessment for which biokinetic studies are crucial.We evaluated the biodistribution of AuNPs ($20 nm) with different surface coatings: citrate, 11-MUA and 3 pentapeptides, CALNN, CALND and CALNS, after i.v. administration to rats (0.6-1 mg Au/kg). Biodistribution was evaluated based on Au tissue content measured by GFAAS.Citrate-AuNPs were rapidly removed from circulation with 60% of the injected dose depositing in the liver. Thirty minutes post-injection, the lungs presented about 6% of the injected dose with levels decreasing to 0.7% at 24 h. Gold levels in the spleen were of 2.6%. After 24 h, liver presented the highest Au level, followed by spleen and blood.A similar biodistribution profile was observed for MUA-coated AuNPs compared to Cit-AuNPs at 24 h post-injection, while significantly higher levels of peptide-capped AuNPs were found in the liver (74-86%) accompanied by a corresponding decrease in blood levels.TEM analysis of liver slices showed AuNPs in Kupffer cells and hepatocytes, trapped inside endosomes. Our data demonstrate that AuNPs are rapidly distributed and that the liver is the preferential accumulation organ. Peptide capping significantly increased hepatic uptake, showing the influence of AuNPs functionalization in biodistribution.

J. Neurochem. (2011) 117, 797–811. Abstract In healthy motor endplates, tetanic depression is overcome by tonic adenosine A2A‐receptor‐mediated facilitation of transmitter release. The A2A receptor operates a coordinated shift from fast‐desensitizing Cav2.1 (P/Q) calcium influx to long‐lasting CaV1 (L) channels on motor nerve terminals. This study aimed at investigating whether A2A receptors‐operated Ca2+ influx via CaV1 (L)‐type channels contribute to sustain acetylcholine release evoked by 50 Hz‐bursts in toxin‐induced Myasthenia gravis (TIMG) rats. In contrast to control animals, inhibition of [3H]acetylcholine (ACh) release by the CaV2.1 (P/Q) channel blocker, ω‐Agatoxin IVA (100 nM), in TIMG rats had a higher magnitude than that observed with the CaV1 (L) channel blocker, nifedipine (1 μM). Adenosine deaminase (0.5 U/mL) and the A2A receptor antagonist, ZM 241385 (50 nM), decreased [3H]ACh release by a similar amount in control rats, but their effects were smaller in magnitude in myasthenic animals. The adenosine precursor, AMP (100 μM), increased (∼40%) ACh release in both control and TIMG animals. Blockade of A2A, but not of A1, receptors prevented AMP‐induced facilitation of transmitter release; nifedipine (1 μM) mimicked the effect of the A2A receptor antagonist. Video‐microscopy studies designed to measure real‐time transmitter exocytosis using the FM4‐64 fluorescent dye fully supported radiochemical data. Thus, impairment of the adaptive shift from CaV2.1 (P/Q) to CaV1 (L) channels may contribute to tetanic failure in myasthenic rats. This parallels the reduction of adenosine A2A receptor tonus in TIMG animals, which might be restored by exogenous application of AMP.