Dr. Chen Explains Singletto Technology and Terms: Photodynamic Therapy (PDT), Light-Activated Dyes, and Singlet Oxygen.

Interview with James Chen, MD, on the WHO consortium’s DeMaND Study.

‍Photodynamic Therapy (PDT) in a New Light  

With thirty years of experience in the application of PDT in diverse areas, including oncology, ophthalmology, dermatology, obesity, and for inflammatory conditions, Dr. James (Jim) Chen has made the study of Photodynamic Therapy (PDT) his passion and his purpose. Now, it is the key to Singletto's mission. As Singletto's Chief Scientific Officer, he is the lead innovator and inventor of Singletto's pending patents.

In this piece, we talk with neurosurgeon Jim Chen about his career working in Photodynamic Therapy.  

Q. Photodynamic Therapy may be a new term to some. Will you provide a simple explanation?

A. Scientifically, we are talking about the way light interacts with special colored dye molecules to create a different type of energy form.

Every day our bodies are interacting with light in powerful ways. If you have ever been suntanned, you have experienced the interaction between sunlight and certain skin cells, which produces melanin causing the skin's darkening. Our ability to see is another example of the interaction between light and biomolecules in the retina which is in the back of the eye.

Photodynamic Therapy then harnesses this power of light to activate certain dyes called photosensitizers to create energy. It’s as simple as that.

Q. Tell us more about the role of photosensitizers in Photodynamic Therapy.  

A. Light is made up of packets of energy called photons. These packets are capable of interacting with certain types of molecules and biomolecules in the environment and in our cells. Only certain molecules can absorb light energy. These are called photosensitizers. They can be naturally occurring, like in our bodies or plants, or can occur in the form of light-activated dyes (LADs). LADs are a special class of compounds capable of absorbing light.

Some interactions between light and certain LADs result in the production of singlet oxygen, a variant of the oxygen we breathe. LADs in their normal, or ground, state are stable. When they are energized by light, they seek to give off the energy to the surrounding environment. Oxygen can accept the energy, allowing the dye to go back to its ground state. Once stable again, the LAD can then accept more energy from light, and the process repeats. This ongoing process creates shorts bursts of energized oxygen called singlet oxygen.  

Singlet oxygen is a by-product of many processes in our cells. It enables our cells to function normally. It is produced all the time in almost all cells of the human body.

Though its created all the time in the body, it is typically quenched (meaning its function is reduced) by interaction with other molecules. We can increase the amount of singlet oxygen produced through Photodynamic Therapy and focus it or confine it to targeted areas. In this way, we can use singlet oxygen to destroy bacteria and viruses.  

Q. Singlet oxygen occurs naturally in our cells and in plants. What are some examples of photosensitizers that create singlet oxygen?  

A. Citrus fruits, such as grapefruit and oranges, contain naturally occurring compounds called psoralens, which can create singlet oxygen when exposed to UV light. Many natural foods we consume actually contain psoralens, including celery, figs, parsley, and parsnips. There has been great success in medical care using derived compounds based on psoralens to treat psoriasis patients.  

Curcumin occurs in the turmeric root and produces singlet oxygen when exposed to UV light or blue light. Singlet oxygen generated from curcumin has been tested for treatment of pancreatic cancer.

Paprika has been shown to create singlet oxygen. Riboflavin, or Vitamin B2, which exists in milk, vitamins, and many foods, also produces singlet oxygen when exposed to light.

It’s important to differentiate these photosensitizers from most of the light-activated dyes used in medicine, however. Though many plants create singlet oxygen naturally, that doesn’t mean they are necessarily used medically for such.  

Q. Can you provide examples of common photosensitizers, or light-activated dyes, currently used in medicine?

A. Porfimer sodium (Photofrin) is an FDA-approved LAD used to treat certain esophagus and lung cancers. Aminolevulinic acid (ALA or Levulan) is a topical LAD used to treat skin conditions on the face or scalp. Foscan is an approved European LAD used in the treatment of head and neck cancers. In Japan, the LAD Laserphyrin treats a variety of cancers. Hexvix is another LAD that helps diagnose bladder cancers.

In Europe, Methylene Blue tablets are utilized as LADs for plasma disinfection, having been shown to destroy bacteria and viruses within such. The LAD Riboflavin is also used for similar plasma disinfection in Latin America and elsewhere.

Q. You have worked in Photodynamic Therapy for over three decades. How did neurosurgery lead you to PDT?

A. I began looking into Photodynamic Therapy as a treatment method for my patients with malignant brain tumors. I was aware of early research showing the positive effects of PDT on cancer. I began doing lab experiments back in the early 90s to test some theories and learn more about PDT. We have certainly come a long way in the science since then. It was interesting to be around for the transition from Kodak projector light sources to higher-tech fiber-optic lasers, as the light source used to activate the dyes. These made it possible to transmit light to deep areas of the brain with minimal invasiveness. Instead of a major operation, I thought that this technique could be used as a minimally invasive procedure, reducing complications and infections. I realized that the number of people I could help by creating technology could far outnumber the actual number of patients for whom I could help by way of operations. So, my day-to-day went from brain and spinal cord surgeries to creating technologies to improve the  health and wellness of populations. Now, the application of this technology has the impact of reaching every single person in the world.

Q. How many current PDT patents do you have, and how many more in the application process?

A. We have recently applied for seven provisional patents related to Singletto technology. I believe I have over 200 additional patents worldwide related to Photodynamic Therapy.

Q. Earlier this year, you had the hypothesis that Photodynamic Therapy could be used to decontaminate hospital masks and equipment infected with COVID-19. Tell us about this.  

A. The genesis of my idea to test LADs on COVID-19 came from the acute emergency need to disinfect PPE (personal protective equipment). This was, of course, driven by the massive, unfortunate shortage of supplies. Healthcare workers, including my family members, were being forced to reuse masks. One family member of mine was actually using a child-sized mask for weeks. I found this situation to be ludicrous and unconscionable. I knew our healthcare workers needed better sterilization techniques and decontamination methods. I just began thinking about all of the research I had read over the years demonstrating the uses of PDT, including its use as a microbial disinfectant, and I believed it could possibly decontaminate SARS-CoV-2.  

Q. What made you think Methylene Blue would be the right photosensitizer, or LAD, for this?

A. Existing data, including clinical use, has demonstrated Methylene Blue's anti-viral and anti-bacterial disinfection capabilities in plasma sterilization. Methylene Blue has an excellent safety profile. It is approved by the FDA for intravenous use in treating Methemoglobinemia. It is commonly used off-label in a variety of applications. Interestingly enough, when I first began experimenting with light-activated dyes back in the early 90s, Methylene Blue was the first LAD I tested. It worked then … and I had a gut feeling it would work on COVID-19. Plus, I knew it was widely available and affordable.

Q. Your theory was tested as part of the World Health Organization’s consortium studying mask decontamination methods. Now that the study has been released, what do you consider the biggest takeaways?

A. The results of the study are clear. Methylene Blue is very effective at disinfecting SARS-CoV-2 and surrogate viruses on personal protective equipment (PPE). We should immediately be able to offer health care workers and the general public a new way to continuously disinfect the virus where it matters – close to their nose and mouth where we know transmission occurs.

Not only can this technology destroy COVID-19, but it can also provide protection from common colds, seasonal flu, and future pathogens, as well. There is great potential for this research and technology to become widely applied to benefit our lives.

Q. Finally, for people who haven't yet heard of Singletto, can you describe the following in one word:

-Singletto Culture: Teamwork. We have a powerful team with great chemistry.

-Singletto People: Selfless. Tirelessly working on solutions that will improve the quality of life.

-Singletto Technology: Innovative. We are taking complex chemical processes and enabling such to work in very simple ways.

-Singletto Innovation: Natural. At the root of this innovation, it is important to recognize these biological and chemical reactions occur all around us, every day. Nature is a great teacher.

-Singletto Mission: Safety. We advocate for safe and proven solutions for you to protect yourself, your family, and others.