Nanotechnology Derived Nanoparticles

Nanotechnology is a cross-disciplinary field, which involves the ability to design and exploit the unique properties that emerge from man-made materials ranging in size from 1 to greater than 100 nm.16 Indeed, the physical and chemical properties of materials—such as porosity, electrical conductivity, light emission, and magnetism—can significantly improve or radically change as their size is scaled down to small clusters of atoms. These advances are beginning to have a paradigm-shifting impact not least in experimental (e.g., thermal tumor killing) and diagnostic oncology.16,32 Examples include superparamagnetic iron oxide nanocrystals, quantum dots (QDs), inorganic nanoparticles, and composite nanoshells. The surfaces of these entities are amenable to modification with synthetic polymers (to afford long-circulating properties) and/or to targeting ligands. However, a key problem with these technologies is toxicity and is discussed elsewhere.16 Iron oxide nanocrystals are formed from an inner core of hexagonally shaped iron oxide particles of approximately 5 nm, which express correlated electron behavior; at a high enough temperature, they are superparamagnetic.33,34 In addition, dextran or synthetic polymers such as poly(ethyleneglycol) surround the crystal core. Indeed, it is the combination of the small size and surface characteristics that allow iron oxide nanocrystals, once injected into the blood stream, to bypass rapid detection by the body's defence cells and accumulate in tumor sites by extravasation. Therefore, they are useful for patient selection, detection of tumor progression, and tracking of the effectiveness of anti-tumor treatment regimens by magnetic resonance imaging (MRI). These approaches can be extended for site-specific imaging of tumor vasculature with targeting ligands. In addition, iron oxide nanocrystals can slowly extravasate from the vasculature into the interstitial spaces, from which they are transported to lymph nodes by way of lymphatic vessels.34 Within lymph nodes they are captured by local macrophages, and their intracellular accumulation shortens the spin relaxation process of nearby protons detectable by MRI. On magnetic resonance images, those node regions accumulating iron oxide appear dark relative to surrounding tissues. Indeed, iron oxide nanocrystals can distinguish between normal and tumor-bearing nodes and reactive and metastatic nodes.34

QDs are made of semiconductors like silicon and gallium arsenide.35,36 In these particles there are discrete electronic energy levels (valance band and conduction band), but the spacing of the electronic energy levels (band gap) can be precisely controlled through variation in size. When a photon, with higher energy than the energy of the band gap, hits a QD, an electron is promoted from valance band into the conduction band, leaving a hole behind. Electrons emit their excess energy as light when they recombine with holes. Since optical response is due to the excitation of single electron-hole pairs, the size and shape of QDs can be tailored to fluoresce specific colors. The ability of QDs to tune broad wavelength together with their photostability is of paramount importance in biological labeling.35,36 Indeed, QDs stay lit much longer than conventional dyes used for imaging and tagging purposes and therefore have the potential to improve the resolution of tumor cells to the single cell level by optical imaging as well as determining heterogeneity among cancer cells in a solid tumor.37-39 Unlike QDs, where optical response is due to the excitation of single electron hole pairs, in metallic nanoparticles (e.g., gold) incident light can couple to the plasmon excitation of the metal. This involves the light-induced motion of all valence electrons.36 Therefore, the type of plasmon that exists on a surface of a metallic nanoparticle is directly related to its shape and curvature; so it is possible to make a wide range of light scatterers that can be detected at different wavelengths. Composite nanoshells consist of a spherical dielectric core (e.g., silica) surrounded by a thin metal shell (e.g., gold). Again, by controlling the relative thickness of the core and shell layers of the composite nanoparticle, the plasmon resonance and the resultant optical absorption properties can be tuned from near-UV to the mid-infrared. Of particular interest is the ability of near-infrared light (700-1000 nm) to penetrate through tissue at depths of a few cm with minimal heat generation and tissue damage. Thus, a recent study demonstrated rapid irreversible photothermal ablation of tumor tissue in vivo following administration of near-infrared-absorbing silica-gold nanoshells in combination with an extracorporeal low-power diode laser.40

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