https://www.msn.com/en-us/health/ot...s-and-multiple-sclerosis-symptoms/ar-BB1ihtur
Potential pharmaceutical/industrial demand vector for gold?
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Hope may be in sight for the millions of Americans who suffer with multiple sclerosis and Parkinson's disease after successful phase two clinical trials left researchers "cautiously optimistic."
The treatment, tested by researchers at the University of Texas Southwestern Medical Center, comes from an unlikely source: suspended nanocrystals of gold.
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In their study, published in the Journal of Nanobiotechnology and funded by Clene Nanomedicine, the team recruited 11 patients with relapsing MS and 13 with Parkinson's for two phase two clinical trials. The participants were first scanned with an MRI machine to establish their baseline levels of key energy metabolites in their brains. In other words, molecules that can be used as a proxy to determine levels of energy production in the brain.
For the following 12 weeks, the participants were given a daily dose of gold nanocrystals before receiving a second brain scan. Among those with Parkinson's, participants saw an average 10.4 percent increase in essential markers for energy metabolism compared to their baseline levels. Patients also reported improved motor function, suggesting that the intervention may relieve some of the functional symptoms of the disease.
No adverse side effects were reported by any of the patients.
"We are cautiously optimistic that we will be able to prevent or even reverse some neurological disabilities with this strategy," Sguigna said in a statement.
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Colloidal gold is a sol or colloidal suspension of nanoparticles of gold in a fluid, usually water.[1] The colloid is coloured usually either wine red (for spherical particles less than 100 nm) or blue-purple (for larger spherical particles or nanorods).[2] Due to their optical,[3] electronic, and molecular-recognition properties, gold nanoparticles are the subject of substantial research, with many potential or promised applications in a wide variety of areas, including electron microscopy, electronics,[4] nanotechnology, materials science,[5] and biomedicine.[6][7][8][9]
The properties of colloidal gold nanoparticles, and thus their potential applications, depend strongly upon their size and shape.[10] For example, rodlike particles have both a transverse and longitudinal absorption peak, and anisotropy of the shape affects their self-assembly.[11]
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Synthesis
Generally, gold nanoparticles are produced in a liquid ("liquid chemical methods") by reduction of chloroauric acid (H[AuCl4]). To prevent the particles from aggregating, stabilizing agents are added. Citrate acts both as the reducing agent and colloidal stabilizer.
They can be functionalized with various organic ligands to create organic-inorganic hybrids with advanced functionality.[17]
Turkevich method
This simple method was pioneered by J. Turkevich et al. in 1951[107][108] and refined by G. Frens in the 1970s.[109][110] It produces modestly monodisperse spherical gold nanoparticles of around 10–20 nm in diameter. Larger particles can be produced, but at the cost of monodispersity and shape. In this method, hot chloroauric acid is treated with sodium citrate solution, producing colloidal gold. The Turkevich reaction proceeds via formation of transient gold nanowires. These gold nanowires are responsible for the dark appearance of the reaction solution before it turns ruby-red.[111]
Capping agents
A capping agent is used during nanoparticle synthesis to inhibit particle growth and aggregation. The chemical blocks or reduces reactivity at the periphery of the particle—a good capping agent has a high affinity for the new nuclei.[112] Citrate ions or tannic acid function both as a reducing agent and a capping agent.[113][114] Less sodium citrate results in larger particles.
Brust-Schiffrin method
This method was discovered by Brust and Schiffrin in the early 1990s,[115] and can be used to produce gold nanoparticles in organic liquids that are normally not miscible with water (like toluene). It involves the reaction of a chlorauric acid solution with tetraoctylammonium bromide (TOAB) solution in toluene and sodium borohydride as an anti-coagulant and a reducing agent, respectively.
Here, the gold nanoparticles will be around 5–6 nm.[116] NaBH4 is the reducing agent, and TOAB is both the phase transfer catalyst and the stabilizing agent.
TOAB does not bind to the gold nanoparticles particularly strongly, so the solution will aggregate gradually over the course of approximately two weeks. To prevent this, one can add a stronger binding agent, like a thiol (in particular, alkanethiols), which will bind to gold, producing a near-permanent solution.[117][118] Alkanethiol protected gold nanoparticles can be precipitated and then redissolved. Thiols are better binding agents because there is a strong affinity for the gold-sulfur bonds that form when the two substances react with each other.[119] Tetra-dodecanthiol is a commonly used strong binding agent to synthesize smaller particles.[120] Some of the phase transfer agent may remain bound to the purified nanoparticles, this may affect physical properties such as solubility. In order to remove as much of this agent as possible, the nanoparticles must be further purified by soxhlet extraction.
Perrault method
This approach, discovered by Perrault and Chan in 2009,[121] uses hydroquinone to reduce HAuCl4 in an aqueous solution that contains 15 nm gold nanoparticle seeds. This seed-based method of synthesis is similar to that used in photographic film development, in which silver grains within the film grow through addition of reduced silver onto their surface. Likewise, gold nanoparticles can act in conjunction with hydroquinone to catalyze reduction of ionic gold onto their surface. The presence of a stabilizer such as citrate results in controlled deposition of gold atoms onto the particles, and growth. Typically, the nanoparticle seeds are produced using the citrate method. The hydroquinone method complements that of Frens,[109][110] as it extends the range of monodispersed spherical particle sizes that can be produced. Whereas the Frens method is ideal for particles of 12–20 nm, the hydroquinone method can produce particles of at least 30–300 nm.
Martin method
This simple method, discovered by Martin and Eah in 2010,[122] generates nearly monodisperse "naked" gold nanoparticles in water. Precisely controlling the reduction stoichiometry by adjusting the ratio of NaBH4-NaOH ions to HAuCl4-HCl ions within the "sweet zone," along with heating, enables reproducible diameter tuning between 3–6 nm. The aqueous particles are colloidally stable due to their high charge from the excess ions in solution. These particles can be coated with various hydrophilic functionalities, or mixed with hydrophobic ligands for applications in non-polar solvents. In non-polar solvents the nanoparticles remain highly charged, and self-assemble on liquid droplets to form 2D monolayer films of monodisperse nanoparticles.
Nanotech studies
Bacillus licheniformis can be used in synthesis of gold nanocubes with sizes between 10 and 100 nanometres.[123] Gold nanoparticles are usually synthesized at high temperatures in organic solvents or using toxic reagents. The bacteria produce them in much milder conditions.
Navarro et al. method
For particles larger than 30 nm, control of particle size with a low polydispersity of spherical gold nanoparticles remains challenging. In order to provide maximum control on the NP structure, Navarro and co-workers used a modified Turkevitch-Frens procedure using sodium acetylacetonate as the reducing agent and sodium citrate as the stabilizer.[124]
Sonolysis
Another method for the experimental generation of gold particles is by sonolysis. The first method of this type was invented by Baigent and Müller.[125] This work pioneered the use of ultrasound to provide the energy for the processes involved and allowed the creation of gold particles with a diameter of under 10 nm. In another method using ultrasound, the reaction of an aqueous solution of HAuCl4 with glucose,[126] the reducing agents are hydroxyl radicals and sugar pyrolysis radicals (forming at the interfacial region between the collapsing cavities and the bulk water) and the morphology obtained is that of nanoribbons with width 30–50 nm and length of several micrometers. These ribbons are very flexible and can bend with angles larger than 90°. When glucose is replaced by cyclodextrin (a glucose oligomer), only spherical gold particles are obtained, suggesting that glucose is essential in directing the morphology toward a ribbon.
Block copolymer-mediated method
An economical, environmentally benign and fast synthesis methodology for gold nanoparticles using block copolymer has been developed by Sakai et al.[127] In this synthesis methodology, block copolymer plays the dual role of a reducing agent as well as a stabilizing agent. The formation of gold nanoparticles comprises three main steps: reduction of gold salt ion by block copolymers in the solution and formation of gold clusters, adsorption of block copolymers on gold clusters and further reduction of gold salt ions on the surfaces of these gold clusters for the growth of gold particles in steps, and finally its stabilization by block copolymers. But this method usually has a limited-yield (nanoparticle concentration), which does not increase with the increase in the gold salt concentration. Ray et al.[128] improved this synthesis method by enhancing the nanoparticle yield by manyfold at ambient temperature.
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Cracow, 26 June 2024 - Gold particles having the size of billionths of a metre are lethal to cancer cells. This fact has been known for a long time, as has a simple correlation: the smaller the nanoparticles used to fight the cancer cells, the faster they die. However, a more interesting, more complex picture of these interactions is emerging from the latest research, conducted at the Institute of Nuclear Physics of the Polish Academy of Sciences, using a novel microscopic technique.
Smaller kills faster – this is what was previously thought about gold nanoparticles used to fight cancer cells. Scientists thought that small nanoparticles would simply find it easier to penetrate the interior of a cancer cell, where their presence would lead to metabolic disturbances and ultimately cell death. The reality, however, turns out to be more complex, as demonstrated by research carried out by scientists from the Institute of Nuclear Physics of the Polish Academy of Sciences (IFJ PAN) in Cracow, supported by theoretical analysis performed at the University of Rzeszow (UR) and Rzeszow University of Technology.
“Our institute operates a state-of-the-art medical and accelerator centre for proton radiotherapy. So when reports emerged a few years ago that gold nanoparticles could be good radiosensitisers and enhance the effectiveness of this sort of therapy, we started to synthesise them ourselves and test their interaction with cancer cells. We quickly found out that the toxicity of nanoparticles was not always as expected,” says Dr. Eng. Joanna Depciuch-Czarny (IFJ PAN), initiator of the research and first author of an article discussing the results, published in the journal Nano Micro Small.
Nanoparticles can be produced using a variety of methods, yielding particles of different sizes and shapes. Shortly after starting their own experiments with gold nanoparticles, the IFJ PAN physicists noticed that biology does not follow the popular rule that their toxicity is greater the smaller they are. Spherical nanoparticles of 10 nanometres in size, produced in Cracow, turned out to be practically harmless to the glioma cell line studied. However, high mortality was observed in cells exposed to nanoparticles as large as 200 nanometres, but with a star-shaped structure.
Elucidation of the stated contradiction became possible thanks to the use of the first holotomographic microscope in Poland, purchased by IFJ PAN with funds from the Polish Ministry of Science and Higher Education.
A typical CT scanner scans the human body using X-rays and reconstructs its spatial internal structure section by section. In biology, a similar function has recently been performed by the holotomographic microscope. Here, cells are also swept by a beam of radiation, only not high-energy radiation, but electromagnetic radiation. Its energy is chosen so that the photons do not disturb cell metabolism. The result of the scan is a set of holographic cross-sections containing information about the distribution of refractive index changes. Since light refracts differently on the cytoplasm and differently on the cell membrane or nucleus, it is possible to reconstruct a three-dimensional image of both the cell itself and its interior.
“Unlike other high-resolution microscopy techniques, holotomography does not require the preparation of samples or the introduction of any foreign substances into the cells. The interactions of gold nanoparticles with cancer cells could therefore be observed directly in the incubator, where the latter were cultured, in an undisturbed environment, what’s more with nanometric resolution, from all sides simultaneously and practically in real time,” enumerates Dr. Depciuch-Czarny.
The unique features of holotomography allowed the physicists to determine the causes of the unexpected behaviour of cancer cells in the presence of gold nanoparticles. A series of experiments was conducted on three cell lines: two glioma and one colon. Amongst others, it was observed that although the small, spherical nanoparticles easily penetrated the cancer cells, the cells regenerated and even started to divide again, despite the initial stress. In the case of colon cancer cells, the gold nanoparticles were quickly pushed out of them. The situation was different for the large star-shaped nanoparticles. Their sharp tips perforated the cell membranes, most likely resulting in increasing oxidative stress inside the cells. When these cells could no longer cope with repairing the increasing damage, the mechanism of apoptosis, or programmed death, was triggered.
“We used the data from the Cracow experiments to build a theoretical model of the process of nanoparticle deposition inside the cells under study. The final result is a differential equation into which suitably processed parameters can be substituted – for the time being only describing the shape and size of nanoparticles – to quickly determine how the uptake of the analysed particles by cancer cells will proceed over a given period of time,” says Dr. Pawel Jakubczyk, professor at the UR and co-author of the model, and then emphasises: “Any scientist can already use our model at the design stage of their own research to instantly narrow down the number of nanoparticle variants requiring experimental verification.”
The ability to easily reduce the number of potential experiments to be carried out, means a reduction in the costs associated with the purchase of cell lines and reagents, as well as a marked reduction in research time (it typically takes around two weeks just to culture a commercially available cell line). In addition, the model can be used to design better-targeted therapies than before – ones in which the nanoparticles will be particularly well absorbed by selected cancer cells, while maintaining relatively low or even zero toxicity to healthy cells in the patient's other organs.
The Cracow-Rzeszow group of scientists is already preparing to continue their research. New experiments should soon make it possible to extend the model of the interaction of nanoparticles with cancer cells to include further parameters, such as the chemical composition of the particles or further tumour types. Later plans also include supplementing the model with mathematical elements to optimise the efficacy of photo- or proton therapy for indicated combinations of nanoparticles and tumours.
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... that nobody really wants to cure. The money is in the "treatment."Gold nanoparticles kill cancer – but not as thought
Gold particles having the size of billionths of a metre are lethal to cancer cells. This fact has been known for a long time, as has a simple correlation: the smaller the nanoparticles used to fight the cancer cells, the faster they die. However, a more interesting, more complex picture of these...www.eurekalert.org
If these peeps refine their research into a mass use cancer killer, I would think that would drive massive demand for medical gold. Cancer is kind of a big deal!
Gold nanoparticles kill cancer – but not as thought
Gold particles having the size of billionths of a metre are lethal to cancer cells. This fact has been known for a long time, as has a simple correlation: the smaller the nanoparticles used to fight the cancer cells, the faster they die. However, a more interesting, more complex picture of these...www.eurekalert.org
If these peeps refine their research into a mass use cancer killer, I would think that would drive massive demand for medical gold. Cancer is kind of a big deal!
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