Here we systematically examined the effect of nanoparticle size (10-100 nm) and surface chemistry (i.e., poly(ethylene glycol)) on passive targeting of tumors in vivo. We found that the physical and chemical properties of the nanoparticles influenced their pharmacokinetic behavior, which ultimately determined their tumor accumulation capacity. Interestingly, the permeation of nanoparticles within the tumor is highly dependent on the overall size of the nanoparticle, where larger nanoparticles appear to stay near the vasculature while smaller nanoparticles rapidly diffuse throughout the tumor matrix. Our results provide design parameters for engineering nanoparticles for optimized tumor targeting of contrast agents and therapeutics.

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Quantum dots have potential in biomedical applications, but concerns persist about their safety. Most toxicology data is derived from in vitro studies and may not reflect in vivo responses. Here, an initial systematic animal toxicity study of CdSe-ZnS core-shell quantum dots in healthy Sprague-Dawley rats is presented. Biodistribution, animal survival, animal mass, hematology, clinical biochemistry, and organ histology are characterized at different concentrations (2.5-15.0 nmol) over short-term (<7 days) and long-term (>80 days) periods. The results show that the quantum dot formulations do not cause appreciable toxicity even after their breakdown in vivo over time. To generalize the toxicity of quantum dots in vivo, further investigations are still required. Some of these investigations include the evaluation of quantum dot composition (e.g., PbS versus CdS), surface chemistry (e.g., functionalization with amines versus carboxylic acids), size (e.g., 2 versus 6 nm), and shape (e.g., spheres versus rods), as well as the effect of contaminants and their byproducts on biodistribution behavior and toxicity. Combining the results from all of these studies will eventually lead to a conclusion regarding the issue of quantum dot toxicity.

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Use of cholinesterase inhibitors is associated with increased rates of syncope, bradycardia, pacemaker insertion, and hip fracture in older adults with dementia. The risk of these previously underrecognized serious adverse events must be weighed carefully against the drugs' generally modest benefits.

Semiconductor quantum dots (QDs) are a new generation of inorganic probes with advantageous properties over traditional organic-only probes for biological applications. A major hurdle in the use of QDs for biology is the inability of the hydrophobically synthesized QDs to interface with aqueous environments. There have been tremendous advances in the surface modification of hydrophobic QDs. However, none of the current techniques fits all of the criteria for an ideal QD coating for biological applications (e.g., maintain the small size and optical properties of QDs, have low nonspecific binding) while providing cost-effective, easy preparation on a large scale. We developed a highly stable biocompatible coating for the surface of ZnS-capped CdSe QDs that maintains all of the hydrophobiccoated QD optical properties. These QDs are prepared by first coating them with mercaptoundecanoic acid and are further cross-linked with the amino acid lysine in the presence of dicyclohexylcarbodiimide to form a stable hydrophilic shell. The surface contains carboxylic acid and amino functional groups for conjugation to biomolecules. Using a dynamic light scattering method, we found that the hydrodynamic diameter of these surface-modified QDs is approximately 20 nm. We demonstrated the feasibility of preparing >400 mg of the biocompatible QDs and the successful conjugation of proteins onto their surface. Finally, we characterized the QD stability and optical properties in various biologically relevant environments.

IMPORTANCE Antibiotics are frequently and often inappropriately prescribed to patients in nursing homes. These antibiotics pose direct risks to recipients and indirect risks to others residing in the home. OBJECTIVE To examine whether living in a nursing home with high antibiotic use is associated with an increased risk of antibiotic-related adverse outcomes for individual residents.