Particle size, surface coating, and PEGylation influence the biodistribution of quantum dots in living mice.

This study evaluates the influence of particle size, PEGylation, and surface coating on the quantitative biodistribution of near-infrared-emitting quantum dots (QDs) in mice. Polymer- or peptide-coated 64Cu-labeled QDs 2 or 12 nm in diameter, with or without polyethylene glycol (PEG) of molecular weight 2000, are studied by serial micropositron emission tomography imaging and region-of-interest analysis, as well as transmission electron microscopy and inductively coupled plasma mass spectrometry. PEGylation and peptide coating slow QD uptake into the organs of the reticuloendothelial system (RES), liver and spleen, by a factor of 6-9 and 2-3, respectively. Small particles are in part renally excreted. Peptide-coated particles are cleared from liver faster than physical decay alone would suggest. Renal excretion of small QDs and slowing of RES clearance by PEGylation or peptide surface coating are encouraging steps toward the use of modified QDs for imaging living subjects.

The fate and toxicity of Raman-active silica-gold nanoparticles in mice.

Raman spectroscopy is an optical imaging method that is based on the Raman effect, the inelastic scattering of a photon when energy is absorbed from light by a surface. Although Raman spectroscopy is widely used for chemical and molecular analysis, its clinical application has been hindered by the inherently weak nature of the Raman effect. Raman-silica-gold-nanoparticles (R-Si-Au-NPs) overcome this limitation by producing larger Raman signals through surface-enhanced Raman scattering. Because we are developing these particles for use as targeted molecular imaging agents, we examined the acute toxicity and biodistribution of core polyethylene glycol (PEG)-ylated R-Si-Au-NPs after different routes of administration in mice. After intravenous administration, PEG-R-Si-Au-NPs were removed from the circulation by macrophages in the liver and spleen (that is, the reticuloendothelial system). At 24 hours, PEG-R-Si-Au-NPs elicited a mild inflammatory response and an increase in oxidative stress in the liver, which subsided by 2 weeks after administration. No evidence of significant toxicity was observed by measuring clinical, histological, biochemical, or cardiovascular parameters for 2 weeks. Because we are designing targeted PEG-R-Si-Au-NPs (for example, PEG-R-Si-Au-NPs labeled with an affibody that binds specifically to the epidermal growth factor receptor) to detect colorectal cancer after administration into the bowel lumen, we tested the toxicity of the core nanoparticle after administration per rectum. We observed no significant bowel or systemic toxicity, and no PEG-R-Si-Au-NPs were detected systemically. Although additional studies are required to investigate the long-term effects of PEG-R-Si-Au-NPs and their toxicity when carrying the targeting moiety, the results presented here support the idea that PEG-R-Si-Au-NPs can be safely used in living subjects, especially when administered rectally.

In situ TEM studies of metal-carbon reactions.

The reactions which occur between amorphous carbon and a number of first transition metals (Ti, Cr, Fe, Co, Ni, and Cu) have been studied by transmission electron microscopy (TEM). The materials are in thin-film form with the metal layer sandwiched between thicker carbon layers. In four cases, the predominant reaction is the graphitization of the amorphous carbon, at temperatures well below 800 degrees C. This is brought about by the elements themselves in the case of Co and Ni, and by metastable carbides in the case of Fe (Fe3C) and Cr (Cr3C2-x). The Ti-C and Cu-C systems do not exhibit graphitization. For the former, only TiC is produced up to 1000 degrees C, while the carbon does not react at all with copper. In situ TEM studies show the mechanism to be of the dissolution-precipitation type, which is equivalent to the metal-mediated crystallization process for amorphous silicon and germanium. The heat of graphitization is found to be 18-19 kcal/mol-C by differential scanning calorimetry.