Au-NP: High-Resolution Biomarkers as Indicators of Nanotoxicity
APPLICATIONS OF TECHNOLOGY:
• Determining the toxicity and biological effects of nanoparticles
• Assessing health, occupational, and environmental risks of nanomaterials
• Establishing safety standards for the use of nanomaterials in biomedical and clinical applications
• Fine-tuning the size of nanomaterials for clinical use
• Provides a measurement reference for size-dependent effects of nanoparticles on molecular response and signaling events
• Can be expanded for safety evaluations of other nanomaterials
• Can be applied to other physico-chemical properties of nanoparticles
Gold nanoparticles (Au-NP) show promise for use in the clinical context, since they are relatively inert, not overtly toxic to cells and are comparable in size to molecular and cellular structures. Their size, shape, and optical properties make them particularly suitable for in vivo use in the detection and treatment of cancer.
After studying the mechanisms for the interaction, uptake, and metabolism of Au-NPs in the cellular environment, Frank Fanqing Chen of Berkeley Lab has devised a model system through which they can help to shed light on the size-dependent biological effects of nanomaterials in general. Dr. Chen has found, using gene function, promoter, and pathway analyses, that genes respond differently to Au-NP nanoparticles of varying size ranges (for example, in the range between 2 and 10 nm; 20 to 40 nm, and an upper threshold of 80–200 nm). Particular biological pathways are activated or perturbed by nanoparticle size. Nanoparticle size appears to play a role in particle sorting and stress responses, and nanoparticle-specific biomarkers affect cell processes including signaling, apoptosis, inflammation, ubiquitination, and intracellular compartmentalization and transportation. The changes in the biomarkers can be used as indicators or predictors for nanotoxicity.
The model invented at Berkeley Lab has been developed into a quantitative matrix that may help predict the effects on cells of a broad array of nanoparticles. Four dominant patterns of size-dependent gene expression emerge, showing different scaling effects. For example, for genes involved in stress response, there is increased down-regulation when particle size decreases (with 40-80 nm as the upper limit), and for genes involved in processes such as transcription, cell growth, and response to virus, only the 2 nm treatment alters the expression.
Dr. Chen’s method establishes detailed, high-resolution biomarkers and molecular-level profiles that can be used as a reference standard. It provides a listing of biomarkers that can be cited as unavoidably affected by nanoparticles of specific sizes when filing for regulatory approval, and should help fine-tune the size of nanomaterials in the design of medical applications. The Au-NP patterns can also be used to study other physico-chemical properties of nanoparticles, such as surface charge, shape, surface encapsulation/coating, and chemical makeup.
Frank Fanqing Chen
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