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Gold Nanoshell: the Advancing Nanotechnology to Fight Against Cancer

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Gold Nanoshell: the Advancing Nanotechnology to Fight Against Cancer Journal Home Page www.bbbulletin.org BRITISH BIOMEDICAL BULLETIN Original Gold Nanoshell: The Advancing Nanotechnology to Fight Against Cancer Dron P. Modi *1 , Sunita Chaudhary 1, Ragin Shah 1 and Dhrubo Jyoti Sen 2 1Department of Pharmaceutics, Arihant School of Pharmacy & Bio Research Institute, Gujarat Technological University, Uvarsad Square, Sarkhej–Gandhinagar Highway, Post: Adalaj, Dist. Gandhinagar, Gujarat–382421, India 2Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Gujarat Technological University, Arvind Baug, Mehsana– 384001, Gujarat, India A R T I C L E I N F O A B S T R A C T Received 31 July 2013 Received in revised form 10 July 2013 Accepted 19 Aug 2013 It has been almost 40 years since the “cancer war” had been declared. It is now generally believed that personalized medicine Keywords : Nanoshell, is the future for cancer patient management. Gold nanoparticles, Anti–EGFR, nanospheres, nanorods, nanoshells will be discussed in detail Bio conjugation, OCT, regarding their uses in in–vitro assays, ex–vivo and in–vivo SERS Nanoparticles, imaging, cancer therapy and drug delivery. Multifunctionality is Tissue Welding the key feature of nanoparticle–based agents. Targeting ligands, imaging labels, therapeutic drugs, and other functionalities can all be integrated to allow for targeted molecular imaging and molecular therapy of cancer. Gold nanoshells, mainly composed of the silica and gold metal. The antibodies of Anti–Epidermal Growth Factor Receptor is chief component of Gold Nanoshells therapy used to target the cancer cells and to “guide” the Gold nanoshells to detect the cancer cells visually by microscope. The future looks brighter than every at many hurdles remain to be conquered. A multifunctional platform based on gold 1 Corresponding author: Department of nanoparticles, with multiple receptor retargeting, multimodality Pharmaceutics, Arihant School of Pharmacy & Bio Research Institute, imaging and multiple therapeutic entities, holds the promise for a Gujarat Technological University, Uvarsad Square, Sarkhej–Gandhinagar “magic gold bullet” against cancer. In this review, we will Highway, Post: Adalaj, Dist. summarize the current state–of–the–art of gold nanoshells with Gandhinagar, Gujarat–382421, India E-mail address: mechanism in biomedical applications targeting cancer. [email protected] © 2013 British Biomedical Bulletin. All rights reserved Modi et al_______________________________________________________ ISSN-2347-5447 Introduction There is a convenient and specific red colour which has been of considerable clinical need for novel methods for detection utility in consumer–related medical products, and treatment of cancer which offer such as home pregnancy tests. In contrast, the improved sensitivity, specificity and cost– optical response of gold nanoshells depends effectiveness. In recent years, a number of dramatically on the relative size of the groups have demonstrated that photonics– nanoparticle core and the thickness of the based technologies are valuable in gold shell. By varying the relative core and addressing this need. Optical technologies shell thicknesses, the colour of gold promise high resolution, non invasive nanoshells can be varied across a broad range functional imaging of tissue at competitive of the optical spectrum that spans the visible costs. However, in many cases, these and the near infrared spectral regions. technologies are limited by the inherently weak optical signals of endogenous Types of Gold Nano Particles chromophores and the subtle spectral There are many subtypes of gold differences of normal and diseased tissue. nanoparticles based on the size, shape and Over the past several years, there has been physical properties (Figure–2). The earliest increasing interest in combining emerging studied gold nanoparticles are gold optical technologies with the development nanospheres (although not exactly spherical of novel exogenous contrast agents, in a strict sense). Subsequently, nanorods, designed to probe the molecular specific nanoshells, and nanocages have all been signatures of cancer, to improve the reported. Another type of gold based detection limits and clinical effectiveness of nanoparticles, with excellent surface– optical imaging. Several scientists has been enhanced Raman scattering properties demonstrated the use and application of gold (termed “SERS nanoparticles”), will also be nanoshells. Recently, interest has developed discussed in this review. 3,4 In the following in the creation of nanotechnology–based text, the term “gold nanoparticle(s)” will refer platform technologies which couple to a collection of all these subtypes and the molecular specific early detection strategies subtype of gold nanoparticles used in each with appropriate therapeutic intervention study will be specified whenever possible. and monitoring capabilities. With continued development in the synthesis The discovery of the nanoshells was techniques over the last two decades, most of made by Professor Naomi J. Halas and her these gold nanoparticles can now be produced team at Rice University in 2003. In 2003 with well controlled size distribution, Halas was awarded for Best Discovery of sometimes with stunning precision (e.g., 2003 by Nanotechnology. nanocages).5 Composition of Gold Nanoshells Gold Nanoshells Metal nanoshells (Figure–1) area new Optical imaging, include those that type of nanoparticle composed of a dielectric uses gold nanoparticles as the contrast agents, core such as silica coated with an ultrathin has very limited applications in human metallic layer, which is typically gold. 1,2 Gold studies. However, in the near–infrared region nanoshells possess physical properties similar (NIR; 700–900 nm), the absorbance of all bio to gold colloid, in particular, a strong optical molecules reaches minimum which provides a absorption due to the collective electronic relatively clear window for optical imaging. 6 response of the metal to light. The optical By varying the composition and dimensions absorption of gold colloid yields a brilliant of the layers, gold nanoshells can be designed BBB[1][1][2013]023-034 Modi et al_______________________________________________________ ISSN-2347-5447 and fabricated with surface plasmon II. Attach very small (1–2 nm) metal “seed” resonance (SPR) peaks ranging from the colloid to the surface of the nanoparticles via visible to the NIR region. 7 For a given molecular linkages; these seed colloids cover composition of gold nanoshell, the SPR peak the dielectric nanoparticle surfaces with a can be tuned by changing the ratio of the core discontinuous metal colloid layer, size to its shell thickness. III. Grow additional metal onto the “seed” Gold nanoshells with SPR peaks in metal colloid adsorbates via chemical the NIR region can be prepared by coating reduction in solution. silica or polymer beads with gold shells of This approach has been successfully used to variable thickness. 8,9 Silica cores are grown grow both gold and silver metallic shells onto using the Stöber process, the basic reduction silica nanoparticles. Various stages in the of tetraethyl orthosilicate in ethanol. To coat growth of a gold metallic shell onto a the silica nanoparticles with gold in an functionalized silica nanoparticle are shown aqueous environment, a seeded growth in Figure–5. technique is typically used. Small gold nanospheres (2–4 nm in diameter) can be Type–1. Synthesis of Gold nano Particles attached to the silica core using an amine– The original synthesis is a four–step terminated silane as a liner molecule, process in which first, mono dispersed silica allowing additional gold to be reduced until nanoparticles are grown using the Stober the seed particles coalesced into a complete method to produce the spherical dielectric shell. 10 The diameter of the gold nanoshell is cores. The Stober method produces spherical largely determined by the diameter of the silica particles by means of hydrolysis of silica core and the shell thickness can be alkyl silicates and subsequent condensation of controlled through the amount of gold silicic acid in alcoholic solution with an deposited on the surface of the core. ammonia catalyst. In the second step, the Gold nanoshells have also been surface of the silica nanoparticles is synthesized via in–situ gold nanoparticle functionalized by the adsorption of an formation using thermo sensitive core–shell organosilane (3–amino propyl particles as the template. 11,12 The use of triethoxysilane), with its amine tails microgel as the core offers significantly protruding from the surface. In the third step a reduced particle aggregation, as well as solution of gold colloid (1–2 nm in diameter) thickness control of the gold nanoshells using is added to the solution. The gold colloid is electro less gold plating. In one study, a virus produced separately from reduction of scaffold has been used to assemble gold HAuCl 4 by alkaline tetrakis nanoshells. 13 This approach may potentially (hydroxymethyl)–phosphonium chloride, provide cores with a narrower size according to the method of Duff. 15 The gold distribution and smaller diameters (80 nm) particles bond to the organosilane linker via than those of silica. (Figure–3 & 4). the amine group, producing silica nanoparticles with a smattered, uneven gold Synthesis and Bioconjugation coating. 16 A final reduction process is used to The synthetic protocol developed for produce silica nanoparticles with a uniform the fabrication of gold nanoshells
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