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UNC-Chapel Hill PHYS 53 - Study Guide

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Minh, Skipper, AlanWhat are Nanoshells?Nanoshells are very small beads with a dielectric core such as silica surrounded by an ultra-thin metal shell, often composed of gold for biomedical applications (Hirsch). Nanoshells typically range between 5 to 30 nanometers (Hirsch). By carefully engineering the size of both components, scientists can produce nanoshells that absorb or scatter light across a wide spectrum– from ultraviolet range to near infrared. The later is particularly useful in biological environments; 800-1300 nanometers is considered the ‘water window’, a region of high physiological transmissivity, that is optimal for imaging and sensing. These wavelengths can easily penetrate several centimeters of tissue (Alivisatos 67). Making Nanoshells:Nanoshells are developed using an approachthat combines techniques of molecular self-assembly with the reduction chemistry of metalcolloid synthesis. Silica nanoparticles are grown viathe Stober method as the dielectric cores.Organosilane molecules (3-Aminopropyltriethoxysilane) are then adsorbedonto these nanoparticles. These molecules bond tothe surface of the silica nanoparticles, extendingtheir amine groups outward. After isolating thecoated silica particles from residual reactants, asolution of very small gold particles (1–2 nm indiameter) is added. The gold particles bondcovalently to the organosilane linkage moleculesvia the amine group (Oldenburg et al.). Thisscattered layer of gold particles serves as nucleationsites for further reduction of gold onto the silicacore by reduction of gold in a chloroauric acidsolution; as more gold is reduced the surface coatinggrows into a complete shell (Hirsch). Figure 1illustrates the growth of the gold particles on thesilica nanoparticle surface, which is typicallycompleted within a few seconds.Medical Applications of Nanoshells:With regards to medical treatment, nanoshells have particular use in combating cancerous tumorsand are currently in development for treatment in humans. As of right now, the methods using Figure 1: This is an electron micrograph that illustrates the process of the reduction reaction that increases the coverage of gold particles. This is a 120 nm diameter silica core decorated with about 2000 gold nanoparticles in Fig. 1a. (Image retrieved from Oldenburg et al.)Minh, Skipper, Alannanoshells have been prototypically tested only in mice, though with extremely favorable results.Though the environment will be different, the methods will remain constant: using the nanoshells’ special optical properties, the cancerous tumors will be targeted with some form of near-infared (NIR) light which will be converted through the nanoshell intermediate into heat and energy, used to dissipate and destroy the cancerous tissue. Absorbing Radiation in Nanoshells:The reason that nanoshells are favorable in transforming light energy into weaponized heat is dueto its primary structure; namely, the metal colloid shell, most often times gold. Metals are far superior to other elements in manipulating energy due to the way that they handle their electrons.With normal elements like carbon and hydrogen, the electrons they carry are usually restrained inbonds to certain locales and moderately rigid. With metals however, their electrons are free to roam amongst each other, creating a sea of electrons in a manner. Therefore, the electrons in metals are more easily excitable to a higher energy state. As the light emitted strikes the electronson the nanoshell and causes them to become excited, the electrons will oscillate instantly and convert the light energy into thermal motion in moving about and returning to their base energy state. The light that causes the electrons to excite is specific to the size and interspacing of the gold nanoshell, similar to how a spring or wave resonates at a specific oscillation frequency. Thisphenomenon in nanoshells is defined as surface plasmon resonance. Nanoshells are very effective at converting light to heat; studies have shown that nanoshell-treated tumors have had temperature increases of 37.4 ± 6.6°C on NIR exposure for 4-6 minutes, which is well above the damage threshold for cells (Hirsch).Targeting Tumors:There are two primary ways of eliminating cancerous cells with nanoshells. The first involves direct contact between the surface of the cell and the nanoshells. In order to make the nanoshells bind to the surface of the cell, scientists must attach antibodies to the surface of the nanoshell to recognize and bond to the tumor. When about twenty to thirty of these shells are bonded to the cell, the scientists will bombard the subject with light for about 4-5 minutes, the electrons will excite and dissipate enough energy to heat up the environment, in this case the cell and destroy it.The second alternative is to introduce the nanoshells to a phagocyte in order to engulf them. The phagocyte will form an inner macrophage to isolate the nanoshells inside and then gets shipped into the cancer cell as part of routine cellular functions. Inside the cancer cell, the phagocyte is metabolized and transported back out of the cell, but the nanoshells are not metabolized and remain inside the tumor cell. Then the same light treatment is administered and the cell is eliminated from the inside out.Other Applications:Nanoshells potential for cancer treatment is an application that gets a lot of publicly, but there are also other exciting potential applications for nanoshells. One of the excitingMinh, Skipper, Alanapplications of Nanoshells is the delivery of drug molecules at specific times by attaching them to a capsule made of a heat-sensitive polymer (Alivisatos 68). The capsule would release its contents only when gentle heating of the attached nanoshells causes it to deform (Alivisatos 68). Nanoshells can also be used for immunoassays, which are antibody-antigen interactions to detecta specific antigen within a complex mixture and is commonly used in the analysis of a blood specimen (Hirsch). The ELISA test, the most widely used immunoassay, suffers from a few limitations because it relies on either fluorescence or a colorimetric change in solution and it requires a lot of filtration and purification that lengthens the time needed to conduct the completeassay, from 4 to 24 hours (Hirsch). Nanoshells can resolve this problem through a newly developed immunoassay technique that utilizes antibody conjugated, near infrared resonant nanoshells, which


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