(News from Nanowerk) Gold nanoparticles are tiny particles of gold. From drug and gene delivery to photothermal and photodynamic therapies, screening and diagnostic tests, radiation therapy, X-ray imaging and CT scans, these small particles engineered from the precious metal perform a variety of functions. in the biomedical field and hold the potential for the future. applications in medicine.
Konstantin Sokolov, Ph.D., Professor of Imaging Physics, and Aaron Schwartz-Duval, Ph.D., T32 Cancer Nanotech Postdoctoral Fellow, recently published an article on the potential of gold nanoparticles for the treatment of cancer (Advanced sciences, “Prospecting Biomineralization of Cellular Gold Nanoparticles as a Viable Alternative to Pre-Engineered Gold Nanoparticles”). Here they discuss gold nanoparticles, how they work, and next steps in the field.
What are gold nanoparticles?
Sokolov: Gold nanoparticles are very, very small particles of gold – the size of about 1,000th the width of a human hair. Suspended in water, they usually have magnificent bright red colors.
People have been unwittingly using gold particles in art for millennia, such as the 4th-century Roman Lycurgus glass cup. But it wasn’t until the late 1980s and early 1990s that people began to realize that these particles also had potential for medical imaging and therapeutic applications. In fact, gold particles are widely used in a range of diagnostic tests. Pregnancy tests are the most widely used. Those bright lines you see on urine pregnancy tests are produced by a solution of gold nanoparticles. A more recent example is that of several rapid COVID-19 tests, which were also based on this very bright color of gold particles.
How do gold nanoparticles work to treat cancer?
Sokolov: There have been significant efforts, including at MD Anderson, to use gold nanoparticles for the treatment of cancer. One was a collaboration between Rice University and MD Anderson on the use of gold nanoshells for the photothermal treatment of cancer. Another example uses cancer-targeted gold nanoparticles to enhance radiation dose delivery specifically to cancer cells. However, there are very significant physical barriers to the delivery of even very small gold nanoparticles inside the tumor because human tissues are usually very dense. This density can be appreciated by touching the skin and feeling the underlying tissue. So even these tiny objects cannot penetrate deep enough into the tumor and cannot reach all the cancer cells. But now we are rethinking how we can overcome this limitation by repurposing a well-known geological phenomenon of gold biomineralization for cancer therapeutic applications.
What is the biomineralization of gold nanoparticles? How it works?
Schwartz-Duval: When we think of typical mineralization, we think of rock formations or ceramics in high temperature and high pressure environments. Biomineralization, on the other hand, occurs when these formations occur outside of these environments. This is orchestrated by living organisms like cells. In the biomedical field, we tend to think of bones and stones. Bones and kidney stones are both calcium biominerals.
With gold, it’s not really obvious that this would also happen because gold is a rare earth metal. However, living organisms are able to cyclically transform gold from a soluble form to a crystalline form. It’s actually related to how gold nuggets form in nature. When microorganisms, such as bacteria, are near gold or interact with gold, which is normally at a very low concentration in soil, these cells dissolve this gold and concentrate it, forming nuggets. Golden. They can also form gold nanoparticles.
Can gold nanoparticles form in the body?
Schwartz-Duval: Yes, they can. This process can occur in mammalian cells containing gold through biomineralization. Studies have shown that biomineralization of gold particles can occur with every type of cell tissue source. We found that it occurs more with cancer than in normal tissue. Potentially, we could apply this strategy to any cancer that would benefit from radiation therapy.
Humans have been obsessed with gold throughout history for its perceived or actual medicinal properties. Now we are making gold nanoparticles for therapeutics. In the 1920s, there were people developing gold salts – ionic chemical compounds of gold – to treat tuberculosis. Although these compounds were not effective against tuberculosis, they have been found to be sometimes effective in relieving inflammation in people with rheumatoid arthritis.
Interestingly, prolonged treatment with large amounts of gold salts on a rare occasion resulted in a slight “blue” appearance of skin – Chrysiasis which was later found to be due to the formation of gold nanoparticles in the skin macrophages. This is proof of the possibility of biomineralization of gold in a human body.
Drugs based on silver or gold salts were used clinically before researchers realized the clinical potential of gold nanoparticles. However, there was no temporal overlap between these two developments. Gold salts fell into disuse with the development of a better understanding of rheumatoid arthritis and the emergence of more advanced treatments. But we believe there is still great potential in this area of research.
Do gold salts have direct therapeutic benefits?
Sokolov: Gold salts have been shown to suppress inflammation. We hypothesize that they may also normalize the local tumor microenvironment. Essentially, they could suppress the pro-inflammatory tumor environment that is currently known to be one of the main drivers of cancer progression. Importantly, gold salt treatment allows the formation of gold nanoparticles which, as we know, can improve therapeutic interventions by increasing the dose of heat or radiation delivered to cancer cells.
How can growing gold nanoparticles in patients help therapeutic interventions?
Sokolov: Our research is focused on using extremely tiny gold atoms to overcome the physical delivery barriers we talked about at the start and to evenly deliver gold to all tumor cancer cells. Think about it: gold nanoparticles are about 1/1000th of a human hair, but gold atoms are over 100 times smaller than gold nanoparticles or only 1/100,000th of a human hair . It’s incredibly small! In fact, it is ultimately the small size of a drug – just a single atom!
Thus, gold atoms or ions can easily penetrate any human tissue like any other ion involved in our physiology. The trick is that cancer cells accumulate these gold atoms – by mechanisms that are still poorly understood – which are followed by intracellular gold biomineralization to form gold nanoparticles. Then we can use these intracellular gold nanoparticles to very effectively improve photothermal or radiotherapeutic therapies.
During photothermal therapy, external light is used to illuminate the tumor, the light is then absorbed by gold nanoparticles generating excessive heat which kills cancer cells.
We can do the same with radiotherapy. This is all the more exciting because radiation can enter anywhere in the body and is one of the most widely used types of cancer treatment. When the radiation interacts with these gold nanoparticles, a shower of secondary electrons is produced. This means that there is a local increase in radiation dose.
As a result, you can apply less radiation to tissue, but the nanoparticles will amplify the effects of radiation to kill cancer cells and spare surrounding normal tissue. The effect of increased local radiation dose by gold nanoparticles is called radiosensitization. This is what we call a direct approach. We are very fortunate to collaborate with pioneers in this field, including radiation physicist MD Anderson Sang Cho, Ph.D.
Schwartz-Duval: The initial data also showed that gold treatments also have a side effect. After applying our gold treatment, we found that it suppressed pro-cancer signaling, back to normal, within the communication network between different cells. When cancer cells communicate, the signals they send to other cells can turn those cells into cancer-promoting states, and when this gets out of control, cancer grows faster and becomes malignant. However, intracellular gold biomineralization somehow disrupts this pro-cancer transformation, indicating that it may commandeer the signaling network. We believe that this phenomenon could potentially extend to new cancer growth sites such as metastatic formations. Along with Dr. Sokolov, I am currently working with Michael Curran, Ph.D., immunologist MD Anderson, to explore this potential.
What is the next step for your research on the biomineralization of gold nanoparticles?
Sokolov: We are currently working with a team of clinicians and basic scientists to assess the effects of radiation in two very important organ sites. In the next few years, we plan to conduct further studies evaluating the therapeutic efficacy of gold salt treatments for pancreatic and thyroid cancers, which are both inoperable and very devastating cancers. We work with pancreatic cancer surgeon Michael Kim, MD, on pancreatic cancer, and with head and neck surgeon Stephen Lai, MD, Ph.D., on thyroid cancer.
We hope that these studies will provide further evidence of the therapeutic efficacy of this new radiation therapy strategy that may ultimately lead to more effective treatment options for cancer patients affected by these deadly cancers.