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Gold in Medicine


Gold has a long history as a therapeutic agent. Its first usage was in the form of gold particles and colloidal gold, afterward it was made into a soluble salt by alchemists and was suspended in a drinkable solution and recommended as a panacea or a remedy for different ailments including tuberculosis and rheumatoid arthritis.

Gold salt therapy (chrysotherapy) dates back to the late 1800s. Introduced by Heinrich Hermann Robert Koch, a microbiologist who discovered tuberculosis and that gold could inhibit the growth of the tubercle bacillus. Later, the first properly controlled clinical trial using gold salts was performed in the United States and resulted in negative outcomes with reports of treatment toxicity, therefore, treatment was mostly continued in Europe. Nevertheless, Koch, who received the Nobel Peace Prize for Physiology or Medicine in 1905, had opened the door for future work and collaborations that resulted in using gold-based arsenicals and other nanoparticles and gold compounds in chemotherapy and for the treatment of rheumatoid arthritis.

 In medicine today, gold nanoconjugates are studied for their pharmacologic and therapeutic properties. The use of gold nanoconjugates has a wide range of possibilities as an alternative to molecule-based systems due to their physical and chemical properties. These nanogold conjugates behave as gene-regulating agents. Drug carriers, photo responsive therapeutics, and imaging agents that have all been developed and studied in the context of cellular biology.

Gold nanoparticles (AUNPS) of different sizes and shapes have been developed over the last 50 years. AUNPS have various properties, such as optical and electronic properties dependent upon their size and shape, the surface to volume ratio with surfaces that can be readily modified with a ligand containing thiol, phosphine, and amine functional groups that exhibit affinity for gold surfaces. The function groups anchored to the ligands on AUNPS can be used to add additional moieties such as proteins, oligonucleotides, and even antibodies to give AUNPS even more functionality. Such gold nanoconjugates have the ability in the crystallization of materials, programmed assembly and arranging nanoparticles into dimers and trimers on DNA templates, as well as potential in bioelectronics and detection methods. Scientists have recently shown that gold nanoconjugates with functional moieties can readily enter living cells. The potential of using such gold nanoconjugates to enter living cells open a new frontier in using them as cellular and therapeutic agents for gene and drug delivery.

In 2014, Cancer Therapy Adviser reported new findings published in Nanoscale, that a team of researchers developed a new method to kill brain cancer cells using gold nanoparticles. Gold nanoparticles containing cisplatin, a chemotherapy drug, were used to treat a variety of cancers. Cancer cells removed from patients with glioblastoma multiform and grown in vitro were allowed to proliferate before being treated with the gold-cisplatin nanoparticles. After 20O days, all of the cancer cells were completely destroyed-they called this a "Trojan horse" treatment [51].
In an Italian study, researchers used a gold-based drug originally used for the treatment of rheumatoid arthritis, to treat HIV. A gold-based drug was used to treat six monkeys infected with an HIV-like virus. They were able to shrink the "reservoir" of virus-infected CD4 cells.

A new method for non-invasive drug delivery for cancer therapy using light and gold nanoparticles have been discovered. Over the last century, there has been much progress in developing medicine for treating cancer and other diseases, but the dispersion of drugs throughout the body often lowers their effectiveness and can cause damage to healthy tissue. In the past year, Israeli scientists, Alona Shagan and Assistant Professor Boaz Mizrahi have developed a technology that allows drugs to be delivered and released to specific diseased tissues that they are targeting. The method they discovered uses polymer-coated gold nanoparticles that can be combined with the drug itself, such that when light shines on the gold particles, the polymer is melted away and the drug is released to the target tissue.

Bio-medical applications involving photo-triggered materials have great potential, but these methods are rarely used due to the damage caused by high-energy, shortwave light, and the polymer coatings can be toxic. However, the method developed by the Mizrahi team uses near-infrared light (NIR) which has the advantage of melting away the polymer without harming bodily tissues. Furthermore, the polymer material consists of FDA- approved material and is designed with various melting points allowing them to control it with lower energy intensities. This new technology is relatively close to clinical application has many potential medical uses, such as sealing internal and external injuries, temporarily holding tissues during surgery, or as a biodegradable scaffold for growing tissues and organs.

Gold plays a key role in the fight against malaria. A team of researchers from the Singapore University of Technology and Design (SUTD) and Nanyang Technological University (NTU), Singapore, has developed a class of gold- containing molecules that impair the malaria parasite's metabolic function, leading to parasite death. Their findings are published in the journal "Dalton Transactions", despite concerted efforts to eliminate malaria, the deadly disease remains a major health threat to the developing world. The causative agent, a parasite known as Plasmodium, is able to establish and sustain infections in humans, leading to complex clinical manifestations.

DNA from cancer cells have a strong affinity for gold, according to a new study. Researchers from the University of Queensland's Australian Institute for Bioengineering and Nanotechnology have discovered that the methylation patterns of cancer DNA have a strong affinity for gold, whilst DNA methylation patterns of healthy cells do not have such a strong affinity for gold. Previous research has shown that the DNA methylation pattern of healthy cells differ from cancer cells. The "methylscape", or methylation landscape of DNA is the epigenetic change that occurs in DNA as a methyl group is added to the DNA molecule sort of like a "chemical cap". The methylation of DNA in cancer cells causes DNA fragments to fold into SD nanostructures that have an affinity for gold, whereas healthy DNA folds in a different way that doesn't have gold affinity. The researchers have designed a cancer test and tested about 200 samples from cancer patients and have shown 90% accuracy in detecting cancer. The test is simple and fast, producing results in just 10 minutes, and the gold particles change colours depending on whether cancer is present. The work, however, is still preliminary, and much more research is needed before test could be used on patients, but their work is nevertheless very promising.

Gold and graphene are implemented in new ultrasensitive biosensors used for detection of human diseases. Biosensors are now able to detect diseases at the molecular level with near perfect efficiency. Scientists at the University of Minnesota have developed ultrasensitive biosensors to detect disorders related to protein misfolding. The technology works by probing protein structures via plasmon waves to view single layers of protein molecules. This is done by combining single-layer thick graphene and nano- sized gold ribbons. They then can shine light on the single-atom-thick graphene layer and create a sloshing motion of electrons or plasmons in the graphene. When they insert proteins between the graphene and gold layer, they are able to view the single protein layers. Disorders such as Alzheimer’s disease, chronic wasting, and mad cow disease can now be detected based on these methods.

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