Treatment Of Cancer Through Nanotechnology Using Nanoshells Biology Essay


Human beings want to live long healthy, pain-free lives. We will continue to create new ways to do so. Nanotechnology is an emerging technology that can help us along that path. It won't enable humans to shrink, but it can, however help us to modify and create particles that circulate through the body with more control. Increasing the amount of toxic drugs eventually kills the patient .The main reason for this happen is bioavailability. This paper fully explains the way to get drugs to a specific site in the body that is to increase the bioavailability.

If the anticancer drugs are pumped through the body it will kill not only cancer cells but also healthy cells. If we can deliver the drugs directly to the cancer cells, it limits the side effects. This benefit is our motivation. There is a significant clinical need for novel methods for detection and treatment of cancer which offer improved sensitivity, specificity. In recent years, a number of groups have demonstrated that photonics-based technologies are valuable in addressing this need. In this paper we are using the nanoshells for cancer treatment which is more effective compare to other modern technologies

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The body is constantly replacing old cells with new ones .The old damaged cells are deliberately killed. This killing process is called as "apoptosis". Some times however mutations occur. This mutations cause the effect such that some new cells to form when the body does not need them and the old cells don't die. These cells are defined by the name as cancer cells. These cancer cells bypass apoptosis and form a mass of tissue which is known as "tumor". The most common four areas of the body as the location of formation of cancer are prostate, gland, breast, lung and colon. The figure [1] shows the normal cell division and cancer cell division. Not surprisingly the amount spending on the cancer research is very high.

Figure [1]-a->Normal cell division [1] -b->.Cancer cell division


Metal nanoshells are a novel type of composite spherical nano particle consisting of a dielectric core covered by a thin metallic shell which is typically gold. Nanoshells possess highly favorable optical and chemical properties for biomedical imaging and therapeutic applications. By varying the relative dimensions of the core and the shell, the optical resonance of these nano particles can be precisely and systematically varied over a broad region ranging from the near-UV to the mid-infrared. Gold happens to be biocompatible with the human body. It can stay in there without corroding otherwise reacting. Gold an inert metal can absorb a quite a bit of light. In addition to spectral tunability, nanoshells offer other advantages over conventional organic dyes including improved optical properties and reduced susceptibility to chemical/thermal denaturation. Furthermore, the same conjugation protocols used to bind bio molecules to gold colloid are easily modified for nanoshells.

The nanoshells are created by first growing perfect silica (glass) cores and then coating the core with a special amine. Amines are the organic compounds that can be used as "attachment points" for structures. This process of attaching is called as "functionalization". The amines are functionalized to the glass core and these functional molecular groups works best for attaching(glueing) gold particles to the glass core .After that a very small (1-3 nm) metal "seed" colloid to the surface of the nanoparticles via molecular linkages; these seed colloids cover the dielectric nanoparticle surfaces with a discontinuous metal colloid layer. A further reaction involving additional chemicals like potassium carbonate and HAuCl4 in the presence of formaldehyde causes more gold particles to attach creating a shell roughly 10nm thick. The figure [2] shows the TEM images of nanoshells.

Figure [2] - TEM image of gold particles attaching to the outside of silica core.


Gold nanoshells can be made to either preferentially absorb or scatter light by varying the size of the particle relative to the wavelength of the light at their optical resonance of the nanoshell plasmon. In Figure [3], a plot of the core/shell ratio versus resonance wavelength for a silica core/gold shell nano particle resonance wavelength shift as a function of nanoshell composition for the case of a 60nm core gold/silica nanoshell. The extremely agile "tunability" of the optical resonance is a property unique to nanoshells: in no other molecular or nanoparticle structure can the resonance of the optical absorption properties be so systematically designed .

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When dealing with medical applications we are interested in near infra-red wavelength (650-1050nm).Because this is the wavelength that transmit through biological tissue. There is the reason for the near infra red transmit through biological tissue. The body is made up of water. Our goal is to find the best spectral region for optical imaging. This region as it turns out is between 800 and 1300nm and is given the spectral region of "water window". This spectral region best suited for optical bio imaging and bio sensing applications. The optical properties of gold nanoshells, when coupled with their biocompatibility and their ease of bio conjugation, render these nano particles highly suitable for targeted bio imaging and therapeutic applications.

Figure [3]-Optical resonance of gold shell-silica core nanoshells as a function of their core/shell ratio.


By controlling the physical parameters of the nanoshells, it is possible to engineer nanoshells which primarily scatter light as would be desired for many imaging applications, or alternatively, to design nanoshells which are strong absorbers permitting photo thermal-based therapy applications. The tailoring of scattering and absorption cross-sections is demonstrated in Figure(4) which shows sample spectra for two nanoshell configurations, one designed to scatter light and the other to preferentially absorb light. Nanoshells can be used to cook cancer cells (absorbing) but they can also be used for imaging(scattering).


Figure [4]-a->a scattering configuration (Core radius-40nm, shell thickness-20nm).-b->an absorbing configuration. (Core radius-50nm, shell thickness-10nm).

Antibody Conjugation:

The gold plated nanoshells are used for medical applications by attaching antibodies to the outside surface. Antibodies are the body's way of detecting and flagging the presence of foreign substances that is cancer cells. Scientists can now use known cancer cells to create mass produced, protein based antibodies. These antibodies can then be attached to the outside of our gold-plated nanoshells which, when they are injected into the body, then attach themselves to these specific cancer cells and only to cancer cells. Ortho-pyridyl-disulfide-n-hydroxysuccinimide polyethylene glycol polymer (OPSS-PEG-NHS, MW=2000) was used to tether antibodies onto the surfaces of gold nanoshells. Excess, unbound polymer was removed by membrane dialysis (MWCO = 10,000). PEGylated antibody (0.67 mg/mL) was added to nanoshells (~109 nanoshells/mL) for 1 hr to facilitate targeting. Unbound antibody was removed by centrifugation at 650G, supernatant removal, and re suspension in potassium carbonate (2 mM). Following antibody conjugation, nanoshells surfaces were further modified with PEGthiol (MW=5000, 1 M) to block non-specific adsorption sites and to enhance biocompatibility.

Figure [5] ->amines with some gold particles. Figure [6] ->the final nanoshell with gold coated core.


After attaching the antibodies, the nanoshells takes a few hours to circulate through the body. Nanoshells are termed as a miniature "thermal scalpels" that can literally cook cancer cells to death. The operating principle here is that these nanoshells will become hot when irradiated with a relatively low-intensity near infrared laser light. The nanoshells can transfer this thermal energy to tumor cells and kill them. Thus, if the nanoshells are targeted to tumor cells, they may enable physicians to first image the tumors and then kill them by turning up the light intensity. Gold nanoshells owe their optical properties to plasmons, ripples of waves in the ocean of electrons flowing across the surface of metallic nano structures. The type of plasmon that exists on a surface of a nanoscale object is directly related to its geometric structure - the precise curvature of a nanoscale gold sphere or a nano-sized pore in metallic foil. When light of a specific frequency strikes a plasmon that oscillates at a compatible frequency, the energy from the light is harvested by the plasmon, converted into electrical energy that propagates through the nanostructure and eventually converted back to light. Nanoshell-mediated photo thermal destruction of carcinoma cells is demonstrated in figure (8). After laser exposure of 35 W/cm2 for 7 minutes, all cells within the laser spot underwent photo thermal destruction as assessed using calceinAM viability staining, an effect that was not observed in cells exposed to either nanoshells alone or NIR light alone. In addition, evidence of irreversible cell membrane damage was noted via imaging of the fluorescent dextran dye. This dye is normally impermeable to healthy cells.

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Figure [7] ->nanoshells with antibodies attaching to the tumor surface

Figure [8] ->cancer unaffected by laser treatment, nanoshells attached to the cancer cells, the death of cancer cells with the nanoshell/laser treatment.


In subsequent experiments, live mice were injected with tumor cells, when the tumors reached a particular size, the nanoshells were injected. After six hours, an 808nm laser was used for three minutes to activate the nanoshells. The figure (9) shows the tumor size at day0 (treatment day) and day10. The nanoshell therapy for seven cases shows no sign of the tumor. For those treated only with the laser (without nanoshells, eight cases) and for those left untreated as an experimental control (are cases) the tumors continued to grow.

The graph in figure (10) shows that all mice with nanoshell treatment lived the entire 60 days; those treated only with the laser were enthuanized by day 19, on when the tumor grew to more than 5 percent of the body weight.

Fig[10]-survival rate for mice receiving nanoshelltherapy.Fig[9]-tumor sizes for day 0 and day10

In an animal study absorbing nanoshells (109/ml, 20-50micro lit) were injected intestinally (~5 mm) into solid tumors (~1 cm) in female SCID mice. Within thirty minutes of injection, tumor sites were exposed to NIR light (820 nm, 4 W/cm2, 5 mm spot diameter, <6 min). Temperatures were monitored via phase-sensitive, phase spoiled gradient-echo MRI. Magnetic resonance temperature imaging (MRTI) demonstrated that tumors reached temperatures which caused irreversible tumor damage (T = 37.4 ± 6.6° C) within 4-6 minutes. Controls which were exposed to a saline injection rather than nanoshells experienced significantly reduced average temperatures after exposure to the same NIR light levels (T < 10° C). These average temperatures were obtained at a depth of ~2.5 mm be the surface. The MRTI findings demonstrated good agreement with gross pathology indications of tissue damage. Histological indications of thermal damage including coagulation, cell shrinkage, and loss of nuclear staining were noted in nanoshell-treated tumors; no such changes were found in control tissue.


Combining advances in bio photonics and nanotechnology offers the opportunity to significantly impact future strategies towards the detection and therapy of cancer. Today, cancer is typically diagnosed many years after it has developed usually after the discovery of either a palpable mass or based on relatively low resolution imaging of smaller but still significant masses.

The development of nanoshell bio conjugates for molecular imaging applications are going on and this describes an important new approach to photo thermal cancer therapy. More extensive in vivo animal studies for both cancer imaging and therapy applications are currently underway in order to investigate both the potential and limitations of nanoshell technologies. Additional studies are in progress to more thoroughly assess the bio distribution and biocompatibility of nanoshells used in in-vivo imaging and therapy applications. There is tremendous potential for synergy between the rapidly developing fields of bio photonics and nanotechnology.