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Gold nanoparticles are tiny particles composed of gold. From drug and gene delivery to photothermal and photodynamic treatments to screening and diagnostic exams, in addition to radiation therapy, X-ray imaging, and CT scans, these minute particles constructed from the luxurious metal have many uses in the biomedical sector and contain the feasibility for future utilization in medicine.

Konstantin Sokolov, a Ph.D. and professor of Imaging Physics, alongside Aaron Schwartz-Duval, a postdoctoral fellow with a T32 Cancer Nanotech, recently released a paper on the prospective usage of gold nanoparticles in cancer therapy. In this paper, they review the topic of nanoparticles and their capabilities, as well as the coming developments in the field.

What is the definition of gold nanoparticles?

Sokolov: Gold nanoparticles are incredibly minuscule pieces of gold — about as large as one-thousandth the thickness of a human hair. When suspended in water, they usually appear as a striking bright red hue.

For centuries, gold particles have been used in the art without people really understanding their potential; however, it wasn’t until the late 1980s to early 1990s that it was realized gold particles had medical imaging and therapeutic applications. Today gold particles are used in a variety of diagnostics assays, such as pregnancy tests, where the bright lines that appear on urine tests are due to a gold nanoparticle solution. Another example of gold particle use is in rapid COVID-19 tests, which also rely on the vivid color of gold particles.

What is the process by which gold nanoparticles can be utilized to combat cancer?

Sokolov: There have been substantial attempts to apply gold nanoparticles to cancer therapy, including a joint venture between Rice University and MD Anderson for photothermal cancer therapy with gold nanoshells. Additionally, another method employs cancer-targeted gold nanoparticles to heighten radiation dose delivery to cancer cells. However, the physical obstacles to delivering even small gold nanoparticles into the tumor are considered as human tissues are generally quite dense. This can be easily perceived by touching the skin and feeling the underlying tissue. As such, these minuscule particles cannot go deep enough into the tumor or reach all cancer cells. But now we are exploring the possibility of using the geology phenomenon of gold biomineralization for cancer therapy purposes to get around this issue.

What is the process of biomineralization using gold nanoparticles? How does it function?

Schwartz-Duval: Traditional mineralization takes place in situations of high heat and pressure, whereas biomineralization is the process of mineral formation created by living organisms like cells. Within the biomedical context, we often think of bones and kidney stones, which are both comprised of calcium biominerals.

It may not be clear what would take place with gold because it is a precious metal. However, living beings are capable of processing gold cyclically from a fluid form to a crystalline state. This is how gold nuggets are made in nature. Microorganisms, such as bacteria, that are present near gold or interacting with it, which is usually present at a very low concentration in the earth, will dissolve it and concentrate it into nuggets. Additionally, they can form gold nanoparticles.

Are gold nanoparticles capable of being created within the body?

Schwartz-Duval: It has been established that mammalian cells have the capacity to biomineralize gold particles. Investigations have indicated that this process is more prominent with cancerous cells than with normal tissue. Thus, there is a potential to employ the biomineralization of gold as a radiotherapy treatment for any type of cancer which would have a positive outcome.

Humans have been captivated by gold throughout history, due to either actual or perceived medicinal properties. Now, we create gold nanoparticles to be used as therapeutics. In the 1920s, individuals were developing gold salts, which are ionic chemical compounds of gold, to fight tuberculosis. Even though these compounds were not successful in treating TB, they were observed to alleviate inflammation in those with rheumatoid arthritis. Surprisingly, when high doses of gold salts were administered, there were occasions when a mild condition of “blue” skin, known as Chrysiasis, would appear. This was later found to be a result of gold nanoparticles forming in skin macrophages. Silver therapeutics or gold salt drugs were used in the clinic before the clinical potential of gold nanoparticles was acknowledged. As we progressed into a better understanding of rheumatoid arthritis and the emergence of more advanced treatments, gold salts subsequently fell out of use. Even so, we are convinced that there is still a great amount of potential in this area of research.

Is there any direct therapeutic advantage to using gold salts?

Sokolov: Gold salts have been observed to reduce inflammation. Our hypothesis is that they can also normalize the tumor’s local microenvironment. Basically, these may diminish the pro-inflammatory environment of the tumor, which is known to be one of the main causes of cancer growth. Notably, treatment with gold salts makes it possible to form gold nanoparticles that can boost therapeutic interventions by raising the heat or radiation dose directed at cancer cells.

What are the potential benefits of introducing gold nanoparticles into individuals for therapeutic purposes?

Sokolov: We are investigating utilizing minuscule gold atoms to surpass any physical delivery impediments that were talked about initially and to dispense gold evenly to all cancer cells in the tumor. Consider it: gold nanoparticles are nearly 1/1000th of a human hair, however, gold atoms are more than 100 times littler than gold nanoparticles or simply 1/100,000th of a human hair. This is incredibly miniature! In reality, it is the utmost small size for a medication — just a single atom!

It is possible for gold atoms and ions to enter any human tissue in the same manner as other ions in our physiology. Cancer cells have the ability to absorb these gold atoms, although the mechanisms behind this are yet to be fully comprehended. These gold atoms are accumulated and undergo biomineralization within cells to generate gold nanoparticles. These intracellular gold nanoparticles can then be used to improve photothermal or radiation therapies to a great extent.

In photothermal therapy, the use of an external light source directed to the tumor is employed to activate gold nanoparticles, resulting in the production of heat in high amounts, which is then used to eradicate cancer cells.

Radiation therapy is a very exciting technique since it can penetrate the body, making it one of the most common types of cancer treatments. When the radiation interacts with gold nanoparticles, a secondary electron shower is produced, leading to an increase in the radiation dose. This means that less radiation is needed to target cancer cells while sparing the normal tissues. This process of amplifying the effects of radiation is known as radiosensitization and is a direct-hit approach. We are fortunate to work with MD Anderson radiation physicist, Sang Cho, Ph.D., who is a pioneer in this field.

Schwartz-Duval: The starting data suggested that gold treatments had a secondary impact. After being applied, the gold treatment appeared to inhibit pro-cancer signaling toward a normal state in the communication network between cells. When cancer cells interact with one another, the signals they send out can cause the cells to become cancer-inducing. If this process goes unchecked, cancer will become more aggressive and malignant. Nevertheless, our research has determined that intracellular gold biomineralization interferes with the pro-cancer mutation. We believe this could be useful in inhibiting new cancer developments, such as metastatic formations. I am currently collaborating with MD Anderson immunologist, Michael Curran, Ph.D., and Dr. Sokolov to investigate this potential.

What are the potential future studies related to the biomineralization of gold nanoparticles?

Sokolov: Our research team consisting of clinicians and basic scientists is currently examining the effects of radiation on two significant organs. Over the coming years, our team is planning to explore the effectiveness of gold salt treatments for pancreatic and thyroid cancers. These two cancer types are inoperable and deadly. Collaborating with pancreatic cancer specialist Michael Kim, M.D., we are working on the pancreatic cancer study, while Stephen Lai, M.D., Ph.D., head and neck surgeon, leads the thyroid cancer research.

It is anticipated that these investigations will give additional proof of the therapeutic effectiveness of this novel radiation technique, which in turn may result in more efficient treatment options for those battling these fatal cancers.