In recent years, there has been an enormous surge in medical technology innovations to cure various critical health conditions. Cancer is one such disease for which different kinds of treatments such as precision medicine, radioligand therapy, radiation therapy, immunotherapy, and many more are being tested to provide better results to cancer patients.
Plasma medicine is a recent development that can contribute to minimizing the challenges occurring in cancer treatment. It is a multidisciplinary subject of research that combines plasma physics and chemistry with biology and clinical medicine to launch a new cancer treatment modality.
What is plasma?
Here, the term "plasma" does not mean the blood part. Physical plasma is an ionized gas usually generated in a high-temperature atmosphere.
Along with solids, gases, and liquids, plasma is the fourth
state of matter in physics. It is the least known but most commonly found
fourth state of matter, accounting for more than 99% of the visible universe's
mass. In other words, plasmas are a "cosmic soup" of freely moving
and stationary atoms, molecules, ions, and electrons with a wide range of
densities and temperatures from cold to extremely hot.
Plasma is a highly conductive matter and responds to
magnetic and electric fields, making it a viable energy source. Plasma medicine
involves generating regulated concentrations of certain chemically reactive
species in low-temperature atmospheric pressure and projecting them to
biological targets such as cells and tissues.
Discovery of Plasma Medicine
Plasma medicine was discovered in the mid-1990s when a few
experiments demonstrated that low-temperature plasma (LTP) has effective bactericidal
properties. With the help of these experiments, it was established that the
reactive species produced by LTP, such as reactive oxygen species (ROS) and
reactive nitrogen species (RNS), played a critical role in disinfecting biological
tissues as well as bacteria on the abiotic surface, making it useful for wound
healing.
The sterilizing properties of cold plasma were demonstrated in 1996. According to the BIS Research report on the plasma medicine market, the Physics and Electronics Directorate of the U.S. Air Force Office of Scientific Research (AFOSR) funded a principle research program in 1997 based on the possible use of plasmas in the healing of troops' wounds and the sterilization of abiotic and biotic surfaces.
For the use of LTP in cancer treatment, Friedman and
Keidar were among the pioneering researchers from AFSOR who developed LTP
sources for medical applications and demonstrated that cold plasma selectively
kills cancer cells. The researchers used cold plasma for cancer treatment. They
showed that high doses of plasma lead to necrosis (the death of most or all the
cells in an organ or tissue) of cancer cells, and low doses initiate apoptotic (cell
death with a series of molecular steps) of cancer cells post-treatment.
Various parameters are involved in the process of plasma’s interaction with biological targets such as cells and tissues; therefore, choosing the combinations for obtaining desired results is a very complex and challenging task. However, the recent developments in the healthcare space due to the integration of machine learning and artificial intelligence (AI) have immensely enhanced the prediction accuracy of plasma treatment-induced changes occurring in cellular systems.
For clinical applications, it is essential to precisely project
the desired type and dose of ROS/RNS to the target organ. Therefore, various
characterization tools are used to gain information on the physical (i.e.,
plasma temperature, power, ultraviolet (UV) radiation, electromagnetic field)
and chemical properties (ROS/RNS and any toxic species) of plasmas.
An in-depth analysis of these properties is not only
important for improving the fundamental mechanisms involved in plasma medicine
applications, but it is also essential to control specific biological
responses. The assessment of all risk factors of LTP treatment is an essential factor
to be considered in any pre-clinical trial. Even basic information such as
temperature is critical because it is the essence of the plasma therapy sources
for heat-sensitive biological tissues and the clinical setup for patient
treatment.
With the ongoing studies on the use of plasma medicine as a cancer
treatment, LTP can be considered a potentially emerging therapeutic technique for
cancer treatment due to its unique biophysical comportment.
A few significant advantages of plasma medicine as cancer
treatment compared with conventional therapies are as follows:
·
The ability to originate a large number of
reactive species (ROS/RNS) in human cells is the main cause of cancer cell
death and controls tumor growth.
·
With a high potential for selectivity toward
cancer cells, it is less likely to cause drug-resistance effects and fewer
long-term side effects in cancer patients as used in the clinic.
Conclusion
Some primary clinical trials of low-temperature plasma therapy have been performed on human patients. However, more extensive clinical research still needs to be done for more detailed information on a variety of cancer cell lines. Many parameters such as treatment (or exposure) time, the optimal dosage of plasma inside the tissues, tissue thickness, diffusion and penetration depth of reactive species, and cellular damage distribution in biological matters determine the cell-death and antitumor efficacy of plasma medicine.
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