GOLD NANOPARTICLES- USES

Applications

The range of applications for gold nanoparticles is growing rapidly and includes:

1. Electronics - Gold nanoparticles are designed for use as conductors from printable inks to electronic chips.¹ As the world of electronics become smaller, nanoparticles are important components in the chip design. Nanoscale gold nanoparticles are being used to connect resistors, conductors, and other elements of an electronic chip.
2. Photodynamic Therapy - Near-IR absorbing gold nanoparticles (including gold nanoshells and nanorods) produce heat when excited

- See more at: http://www.sigmaaldrich.com/materials-science/nanomaterials/gold-nanoparticles.html#sthash.yZRWYXkS.dpuf

 DRUG DELIVERY

Applications

The range of applications for gold nanoparticles is growing rapidly and includes:

1. Electronics - Gold nanoparticles are designed for use as conductors from printable inks to electronic chips.¹ As the world of electronics become smaller, nanoparticles are important components in the chip design. Nanoscale gold nanoparticles are being used to connect resistors, conductors, and other elements of an electronic chip.
2. Photodynamic Therapy - Near-IR absorbing gold nanoparticles (including gold nanoshells and nanorods) produce heat when excited

- See more at: http://www.sigmaaldrich.com/materials-science/nanomaterials/gold-nanoparticles.html#sthash.yZRWYXkS.dpuf

Applications

The range of applications for gold nanoparticles is growing rapidly and includes:

1. Electronics - Gold nanoparticles are designed for use as conductors from printable inks to electronic chips.¹ As the world of electronics become smaller, nanoparticles are important components in the chip design. Nanoscale gold nanoparticles are being used to connect resistors, conductors, and other elements of an electronic chip.
2. Photodynamic Therapy - Near-IR absorbing gold nanoparticles (including gold nanoshells and nanorods) produce heat when excited

- See more at: http://www.sigmaaldrich.com/materials-science/nanomaterials/gold-nanoparticles.html#sthash.yZRWYXkS.dpufDrug delivery systemDE Gold nanoparticles can be used to optimize the biodistribution of drugs to diseased organs, tissues or cells, in order to improve and target drug delivery.It is important to realize that the nanoparticle-mediated drug delivery is feasible only if the drug distribution is otherwise inadequate. These cases include drug targeting of difficult, unstable molecules (proteins, siRNA, DNA), delivery to the difficult sites (brain, retina, tumors, intracellular organelles) and drugs with serious side effects (e.g. anti-cancer agents). The performance of the nanoparticles depends on the size and surface functionalities in the particles. Also, the drug release and particle disintegration can vary depending on the system (e.g. biodegradable polymers sensitive to pH). An optimal nanodrug delivery system ensures that the active drug is available at the site of action for the correct time and duration, and their concentration should be above the minimal effective concentration (MEC) and below the minimal toxic concentration (MTC).

Gold nanoparticles are being investigated as carriers for drugs such as Paclitaxel. The administration of hydrophobic drugs require molecular encapsulation and it is found that nanosized particles are particularly efficient in evading the reticuloendothelial system.
Gold nanoparticles are also used to circumvent multidrug resistance (MDR) mechanisms.Mechanisms of MDR include decreased uptake of drugs, reduced intracellular drug concentration by activation of the efflux transporters, modifications in cellular pathways by altering cell cycle checkpoints, increased metabolism of drugs, induced emergency response genes to impair apoptotic pathways and altered DNA repair mechanisms.

• In Ayurveda. More than 1,000 years ago, gold was used as a nanoparticle (swarnabhasma).
• At that time, there were no sophisticated instruments and that is why people did not know that it was a gold nanoparticle.
• gold nanoparticle was bio-compatible, easy to synthesize and multiple cancer drugs could be loaded. It could reduce the toxicity of the anti-cancer drug,
• Scientists are now using an eco-friendly green chemistry approach- via leaf extracts of Bhringaraj (a herbal plant) to create the biocompatible nanoparticles.
• Bhringaraj-extracted bio-compatible gold nanoparticle was used to deliver an anti-cancer drug —Doxorubicin into lung and breast cancer cell lines.
• If you add fluorescent molecule in these gold nanoparticles, it could be used to detect the position of the tumor.

• Tumor detection

  In cancer research, colloidal gold can be used to target tumors and provide detection using SERS (Surface Enhanced Raman Spectroscopy) in vivo. These gold nanoparticles are surrounded with Raman reporters, which provide light emission that is over 200 times brighter than quantum dots. It was found that the Raman reporters were stabilized when the nanoparticles were encapsulated with a thiol-modified polyethylene glycol coat. This allows for compatibility and circulation in vivo. To specifically target tumor cells, the pegylated gold particles are conjugated with an antibody (or an antibody fragment such as scFv), against, e.g. Epidermal growth factor receptor, which is sometimes overexpressed in cells of certain cancer types. Using SERS, these pegylated gold nanoparticles can then detect the location of the tumor.
  Gold nanoparticles accumulate in tumors, due to the leakiness of tumor vasculature, and can be used as contrast agents for enhanced imaging in a time-resolved optical tomography system using short-pulse lasers for skin cancer detection in mouse model. It is found that intravenously administrated spherical gold nanoparticles broadened the temporal profile of reflected optical signals and enhanced the contrast between surrounding normal tissue and tumors.
  
  

  Tumor targeting via multifunctional nanocarriers. Cancer cells reduce adhesion to neighboring cells and migrate into the vasculature-rich stroma. Once at the vasculature, cells can freely enter the bloodstream. Once the tumor is directly connected to the main blood circulation system, multifunctional nanocarriers can interact directly with cancer cells and effectively target tumors.
  Therefore, gold nanoparticles have the potential to join numerous therapeutic functions into a single platform, by targeting specific tumor cells, tissues and organs. Actually, Conde et al. reported the evaluation of the inflammatory response and therapeutic siRNA silencing via RGD-nanoparticles in a lung cancer mouse model. This study reported the use of siRNA/RGD gold nanoparticles capable of targeting tumor cells in two lung cancer xenograft mouse models, resulting in successful and significant c-Myc oncogene downregulation followed by tumor growth inhibition and prolonged survival of the animals. This delivery system can achieve translocation of siRNA duplexesattention and, in particular, small-interference RNA (siRNA) shows importance in novel molecular approaches in the knockdown of specific gene expression in cancerous cells. The major obstacle to clinical application is the uncertainty about how to deliver therapeutic siRNAs with maximal therapeutic impact. Gold nanoparticles have shown potential as intracellular delivery vehicles for siRNA oligonucleotides with maximal therapeutic impact.
  
  

  Regulation of gene expression via siRNA-gold nanoparticles. Engineered nanoparticles modified with siRNA can represent a delivery system of siRNA and a useful tool to block gene function and for sequence-specific post-transcriptional gene silencing. siRNA-modified nanocarriers can enter cells and subsequently unwound siRNA strands and assembled into an effector complex, RNA Induced Silencing Complex (RISC), which can direct RNA cleavage, mediate translational repression or induce chromatin modification. The antisense strand then binds to its complementary/target mRNA (activated RISC/mRNA complex). The catalytic RISC recognizes mRNAs containing perfect or near-perfect complementary sequence to the guide siRNA and cleaves the mRNAs at a site precisely 10 nucleotides from the 5’-end of the guide strand. Finally, mRNA degradation is achieved by endo- and exonucleases, resulting in knockdown of the expression of the corresponding genes.
  Recently, Conde et al. provided evidence of in vitro and in vivo RNAi triggering via the synthesis of a library of novel multifunctional gold nanoparticles, using a hierarchical approach including three biological systems of increasing complexity: in vitro cultured human cells, in vivo freshwater polyp (Hydra vulgaris), and in vivo mice models. The authors developed effective conjugation strategies to combine, in a highly controlled way, specific biomolecules to the surface of gold nanoparticles such as: (a) biofunctional spacers: Poly(ethylene glycol) (PEG) spacers used to increase solubility and biocompatibility; (b) cell penetrating peptides such as TAT and RGD peptides: A novel class of membrane translocating agents named cell penetrating peptides (CPPs) that exploit more than one mechanism of endolecules and even small particles inside the cell for their biological actions; and (c) siRNA complementary to a master regulator gene, the protooncogene c-myc, were bond covalently (thiol-siRNA) and ionically (naked/unmodified siRNA) to gold nanoparticles. ocytosis to overcome the lipophilic barrier of the cellular membranes and deliver large mo directly into the tumour cell cytoplasm and accomplish successful silencing of an oncogene expression. Actually, RGD/siRNA-AuNPs can target preferentially and be taken up by tumor cells via integrin αvβ3-receptor-mediated endocytosis with no cytotoxicity, showing that can accumulate in tumor tissues overexpressing αvβ3 integrins and selectively delivered c-Myc siRNA to suppress tumor growth and angiogenesis.
  

  
  nanoparticles have also shown potential as intracellular delivery vehicles for antisense oligonucleotides (ssDNA,dsDNA) by providing protection against intracellular nucleases and ease of functionalization for selective targeting.^[54][55] Recently, Conde et al. developed a new theranostic system capable of intersecting all RNA pathways: from gene specific downregulation to silencing the silencers, i.e. siRNA and miRNA pathways. The authors reported the development gold nanoparticles functionalized with a fluorophore labeled hairpin-DNA, i.e. gold nanobeacons, capable of efficiently silencing single gene expression, exogenous siRNA and endogenous miRNAs while yielding a quantifiable fluorescence signal directly proportional to the level of silencing. This method describes a gold nanoparticle-based nanobeacon as an innovative theranostic approach for detection and inhibition of sequence-specific DNA and RNA for in vitro and ex vivo applications. Under hairpin configuration, proximity to gold nanoparticles leads to fluorescence quenching; hybridization to a complementary target restores fluorescence emission due to the gold nanobeacons’ conformational reorganization that causes the fluorophore and the gold nanoparticle to part from each other. This concept can easily be extended and adapted to assist the in vitro evaluation of silencing potential of a given sequence to be later used for ex vivo gene silencing and RNAi approaches, with the ability to monitor real-time gene delivery action.^[

  Photothermal agents

  Gold nanorods are being investigated as photothermal agents for in-vivo applications. Gold nanorods are rod-shaped gold nanoparticles whose aspect ratios tune the surface plasmon resonance (SPR) band from the visible to near-infrared wavelength. The total extinction of light at the SPR is made up of both absorption and scattering. For the smaller axial diameter nanorods (~10 nm), absorption dominates, whereas for the larger axial diameter nanorods (>35 nm) scattering can dominate. As a consequence, for in-vivo applications, small diameter gold nanorods are being used as photothermal converters of near-infrared light due to their high absorption cross-sections.^{[citation needed]} Since near-infrared light transmits readily through human skin and tissue, these nanorods can be used as ablation components for cancer, and other targets. When coated with polymers, gold nanorods have been known to circulate in-vivo for greater than 15 hours half-life.^{[citation needed]} Apart from rod-like gold nanoparticles, also spherical colloidal gold nanoparticles are recently used as markers in combination with photothermal single particle microscopy.
  

  Radiotherapy dose enhancer

  Following work by Hainfield et al. there has been considerable interest in the use of gold and other heavy-atom containing nanoparticles to enhance the dose delivered to tumors. Since the gold nanoparticles are taken up by the tumors more than the nearby healthy tissue, the dose is selectively enhanced. The biological effectiveness of this type of therapy seems to be due to the local deposition of the radiation dose near the nanoparticles. This mechanism is the same as occurs in heavy ion therapy.
  

  Detection of toxic gas

  Researchers have developed simple inexpensive methods for on-site detection of hydrogen sulfide H
  2S present in air based on the antiaggregation of gold nanoparticles (AuNPs). Dissolving H
  2S into a weak alkaline buff solution leads to the formation of HS-, which can stabilize AuNPs and ensure they maintain their red color allowing for visual detection of toxic levels of H
  2S.
  

GENE PATENTING

• Gene patent definition. The controversial legal practice of patenting a newly discovered gene. It allows unique segments of DNA, which perhaps code for a certain disease or a certain protein, to be owned by an individual or corporation.
• BRCA1 and BRCA2 human genes used for diagnosing breast and ovarian cancers. (BRCA= BReast CAncer). If a woman has mutation (fault) in BRCA 1 or 2= higher risk of breast/ovarian cancer.
• U.S. Patent and Trademark Office has been awarding patents on genes for about 30 years.
• In the mid-90s, Myriad Genetics ltd. got patents for the BRCA genes.
• Thanks to this patent, Myriad genetics company got monopoly for selling BRCA gene testing. Each test costs >3000$.
• 2009-10: The American Civil Liberties Union (an NGO) challenged this patent in court. Their point= Nobody can “patent” human genes because genes are products of nature.
• 2013: Matter going in US Supreme Court 
• Pros: * Gives companies that patent genes time to look at the genes without competition. These companies do not have to worry that other companies are competing with them to make new discoveries. This is especially important for smaller companies that may not have the financial support to compete with larger, more established companies.
  * Encourages research and development in private industry. Patents support innovation and invention by giving companies rights to gene sequences. The lure of a potential patent drives and pushes researchers to think more creatively and work harder in order to obtain a patent for their work.
  * Provides opportunities for investment in research and development. Companies, as well as individuals, can invest in a patented gene. This provides financial support for the development of useful innovations. It can take hundreds of millions of dollars to introduce a new drug to the market. Most companies do not have this money and rely on investors for financial assistance.
  
  Cons:
  * Hinders research. Since patents give the owners intellectual property rights on the patented genome sequence for 17 to 20 years, many people fear that gene patents hinder research. For example, patents on the BRCA1 and BRCA2 gene variants, which have been linked to inherited breast and ovarian cancers, belong to Myriad Genetics. The patents give Myriad Genetics exclusive rights to conduct diagnostic tests on these genes. This means that other companies are not allowed to work with these genes, missing out on the potential to make important discoveries on these patented genes.
  * Leads to monopolization of genes. Companies that hold gene patents have exclusive rights to them and may decide to not allow other companies to look at these genes. This may lead to a monopoly and foster a secretive culture among research companies.
  * Slows down medical results. If a company holds a gene patent, they own sole rights to research and testing on that gene. So if a patient has a test done on that gene, the samples must be sent to the company owning the gene patent in order to be tested. This could cause delays in getting test results.