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Glossary ADME—stands for “absorption, distribution, metabolism, excretion.” Mnemonic for toxicology studies needed for determining safety of a drug, biologic, or medical device intended for use in the body. albumin—the primary protein in blood plasma. bio-barcode—method developed to improve limits of detection for pro- tein concentrations in samples. By coupling the protein binding events with DNA “barcodes”—unique sequences of DNA matched with specific protein targets (sequences can be random and do not need to be related to the protein)—additional sensitivity is gained because the DNA barcodes can be amplified to detectable levels using polymerase chain reaction. biocompatibility—the degree to which a material or device can perform its function without causing undesirable immune response from the host organism or other adverse effects. biodistribution—the locations to which materials or devices travel after placement in a living body. biomarker—“a characteristic that is objectively measured and evaluated as an indicator of normal biological prcesses, pathogenic processes, or pharmacologic responses to a[n] … intervention” (Biomarkers Definitions Working Group, 2001). Example: cholesterol level. 77

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78 NANOTECHNOLOGY AND ONCOLOGY biomolecule—molecule produced by a living organism, such as a protein, nucleic acid, or other biochemical. cantilever—an object projecting out into open space with support only on one side. A diving board is an example. In microtechnology or nanotech- nology, thin cantilevers composed of various materials can be used for precise measurements, such as in atomic force microscopy and the small mass measuring device discussed in this workshop summary. cellular pumps—membrane protein complexes that transport molecules such as lipids and other biomolecules, drugs, and other chemicals into or out of a cell. Cellular pumps are involved in removing foreign substances from cells, and so adaptations to a particular drug or class or drugs can lead to drug resistance. chemiluminescence—occurs when the energy released from a chemical reaction is in the form of light rather than heat. colorimetric assay—a test used to detect levels of a chemical or biomol- ecule or completion of a chemical or biological reaction using a change in color due to change in pH of an indicator chemical, chemical composition of the reaction solution, or aggregation of colloidal particles. contrast material—substance used during biological imaging to enhance the viewer’s ability to distinguish between features. Contrast materials consist of fluorescent or radioactive molecules or atoms as well as metal- lic or fluorescent nanoparticles. Contrast materials preferentially travel to locations in biological samples based on their chemical and biological properties. cytotoxic—the property of being harmful to the health of cells. dendrimer—a branched polymer whose branching is symmetric. One or more polymers can be used to synthesize a dendrimer, and each com- ponent will affect the properties of the dendrimers. Dendrimers have discrete molecular weights and can have sizes in the nanometer range. dose-related toxicities—harmful effects of substances related to the amount of the substance to which an organism is exposed. ELISA (enzyme-linked immunosorbent assay)—a test which detects pro- teins in solutions by first selectively capturing the proteins out of solu- tion onto a surface and then attaching fluorescent probes to the proteins. ELISA assays often probe many proteins at once using different capture agents in different wells of a microtiter plate.

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79 GLOSSARY endocytosis—process by which cells internalize objects and molecules. epidermal growth factor receptor (EGFR)—a receptor that is overpro- duced in several solid tumors, including breast and lung cancers. Its overproduction is linked to a poorer prognosis because it enables cell proliferation, migration, and the development of blood vessels. Several FDA-approved drugs specifically target EGFR. hemolysis—rupturing of red blood cells. The ability of a substance to cause hemolysis can be evaluated as part of a toxicological assessment of the substance. histopathology—examination of tissue samples in order to understand disease processes in the organism from which the sample was obtained. kinetics—in physics, the study of motion. In chemistry, the study of reac- tion dynamics. leukocyte—white blood cells, which are important components of the immune system. liposomes—small particles constructed from lipid bilayers. A liposome can carry molecules in its interior cavity; the carried molecules are most often water soluble. LMWP (low-molecular-weight peptide)—In the context of this summary, LMWPs are components of blood samples that can potentially be used to develop new medical therapies. MALDI TOF MS (matrix-assisted laser desorption/ionization time-of- flight mass spectrometry)—a type of spectrometry used to identify com- ponents of materials that are difficult to measure by more traditional mass spectrometry methods. magnetic resonance imaging—in this method of imaging, a magnetic field is used to align the magnetic moments of protons in some atoms, such as the hydrogen atoms in water found in body tissues. The decay of the alignment is then measured and used to create images. Differences in contrast are due to differences in chemical properties of tissues. For example, fat has less water than blood, and so they would appear with different intensities on an image. magneto–fluorescent nanoparticles (MFNP)—nanoparticles with both magnetic and fluorescent properties. Such nanparticles can be made from silica infused with both a fluorescent dye and iron oxide nanoparticles.

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80 NANOTECHNOLOGY AND ONCOLOGY micelle—small particle constructed from lipid layers. A liposome can carry molecules in its interior cavity; these molecules are usually hydrophobic. molecular signature—a distinctive set of biomolecules or biochemicals present in the bloodstream or a particular tissue indicating a healthy or disease state. nanobiochip sensor—test consisting of a nano-sized capture well on a polymer base. In a single well, cells are captured, labeled, and imaged, speeding and miniaturizing multiple laboratory processes. nanodevice—a device (medical device in this context) possessing size in the nanometer range or some property dependent on the nanoscale size of a device component. nanodiagnostics—a diagnostic test possessing size in the nanometer range or some property dependent on the nanoscale size of a device component. nanomanufacturing—manufacturing of nanotechnology products. nanomaterials—materials whose size is in the nanometer range or whose components are in the nanometer range. nanomedicine—medical breakthroughs dependent on nanotechnology. nanometer (nm)—one billionth of a meter. A strand of DNA is approxi- mately 2 nm in diameter. nanoparticle—a piece of matter with at least one dimension between about 1 and 100 nm. nanoscale—the size range from about 1 to 100 nm. nanoshell—nanomaterial with a core of silica and a metallic outer layer and can be decorated with molecular probes for cancer-related com- pounds. Nanoshells can be used to image tumors and for theranostics. Nanoshells are also used to provide targeted delivery of drugs to tumor cells. nanostructure—a collection of atoms, molecules, or nanoparticles whose relative positions are engineered chemically or physically on the nano- meter or micron scale. nanotechnology—“the understanding and control of matter at dimen- sions between approximately 1 and 100 nanometers, where unique phe- nomena enable novel applications. Encompassing nanoscale science, engi- neering, and technology, nanotechnology involves imaging, measuring, modeling, and manipulating matter at this length scale” (NNI, 2010).

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81 GLOSSARY nanotoxicity—toxicity of a material resulting from its nanoscale proper- ties as distinguished from the toxicity caused by the same material in bulk form. nanotube—most commonly, this term refers to tubes formed by graphitic sheets of carbon atoms. Carbon nanotubes can be as narrow as just a few nanometers and up to hundreds of microns in length or longer. Car- bon nanotubes can be conducting or semiconducting depending on their atomic arrangement, and individual nanotubes are very strong. nanowire—a wire whose diameter is in the nanoscale range. Nanowires can range from several hundred nanometers in length to many microns and longer. Nanowires can be synthesized or fabricated from many dif- ferent materials. neoplastic—possessing characteristics of abnormal new tissue growth. PEGylated—property of being coated with molecules of polyethylene glycol or functionalized polyethylene glycol. pharmacodynamics—the effects of a drug and its metabolites on a living organism, including how the effects are modified by characteristics of the organism treated with the drug. pharmacokinetics (PK)—the chemical evolution of a drug after admin- istration to a living organism, including lifetimes, metabolic products, biodistribution, and routes of clearance from the organism. phase I clinical trial—a clinical trial in a small number of patients in which the toxicity and dosing of an intervention are assessed. phase II clinical trial—a clinical trial in which the safety and preliminary efficacy of an intervention are assessed. phase III clinical trial—a large clinical trial in which the safety and effi- cacy of an intervention are assessed in a large number of patients. The Food and Drug Administration generally requires new drugs to be tested in phase III trials before they can be put on the market. photolithography—method by which precise patterns are transferred from a master pattern (a mask) onto a substrate. This method is used to fabricate computer chips, for example. quantum dots—nanocrystals made from one or more types of semicon- ducting materials. Quantum dots specifically refer to nanocrystals that fluoresce when excited with light. These nanocrystals are used as imag- ing labels for biological imaging and have several advantages over tra-

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82 NANOTECHNOLOGY AND ONCOLOGY ditional organic fluorescent dyes, including longer fluorescence lifetimes and the ability to fluoresce when excited with a broad range of excitation wavelengths. reticuloendothelial system (RES)—a component of the immune system consisting primarily of macrophages and monocytes. self-assembly—process that occurs when a system—often of similar shape, size, or composition—move from a disordered to a more ordered state as the system approaches equilibrium. Characteristics that work to effect the ordered state include physical and chemical properties such as polarizability, surface charge, and hydrophobicity and forces such as capillary action. target moiety—a part of a molecule that is selected for binding of an antibody or drug for an assay, treatment, or medical device (such as an imaging contrast enhancer). theranostics—molecular complexes that enable both a diagnostic test and delivery of a therapeutic agent simultaneously in a living organism. therapeutic target—the destination for delivery, binding, or therapeutic effect of a drug or other medical treatment. transgenic—possessing, referring to, or being a gene from one species residing in another species. tumor necrosis factor (TNF)—a protein involved in inflammation, it causes cell death, including by causing cell death of tumor cells. xenograft—cells, tissues, or organs that have been transferred from one species to another. REFERENCES Biomarkers Definitions Working Group. 2001. Biomarkers and surrogate endpoints: Pre- ferred definitions and conceptual framework. Clinical Pharmacology and Therapeutics 69(3):89–95. NNI (National Nanotechnology Initiative). 2010. What Is Nanotechnology? http://www.nano. gov/html/facts/whatIsNano.html (accessed January 3, 2011).