In vivo quantum-dot toxicity assessment.

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.

Visualizing quantum dots in biological samples using silver staining.

Quantum dot (QD) based contrast agents are currently being developed as probes for bioimaging and as vehicles for drug delivery. The ability to detect QDs, regardless of fluorescence brightness, in cells, tissues, and organs is imperative to their development. Traditional methods used to visualize the distribution of QDs in biological samples mainly rely on fluorescence imaging, which does not account for optically degenerate QDs as a result of oxidative quenching within the biological environment. Here, we demonstrate the use of silver staining for directly visualizing the distribution of QDs within biological samples under bright field microscopy. This strategy involves silver deposition onto the surface of QDs upon reduction by hydroquinone, effectively amplifying the size of QDs until visible for detection. The method can be used to detect non-fluorescent QDs and is fast, simple, and inexpensive.

Mediating tumor targeting efficiency of nanoparticles through design.

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.

Nanotoxicity: the growing need for in vivo study.

Nanotoxicology is emerging as an important subdiscipline of nanotechnology. Nanotoxicology refers to the study of the interactions of nanostructures with biological systems with an emphasis on elucidating the relationship between the physical and chemical properties (e.g. size, shape, surface chemistry, composition, and aggregation) of nanostructures with induction of toxic biological responses. In the past five years, a majority of nanotoxicity research has focused on cell culture systems; however, the data from these studies could be misleading and will require verification from animal experiments. In vivo systems are extremely complicated and the interactions of the nanostructures with biological components, such as proteins and cells, could lead to unique biodistribution, clearance, immune response, and metabolism. An understanding of the relationship between the physical and chemical properties of the nanostructure and their in vivo behavior would provide a basis for assessing toxic response and more importantly could lead to predictive models for assessing toxicity. In this review article, we describe the assumptions and challenges in the nanotoxicity field and provide a rationale for in vivo animal studies to assess nanotoxicity.