⚡Plasma Medicine Unit 6 – Cancer treatment using plasma

What is Plasma in Medicine?

• Plasma is the fourth state of matter consists of ionized gas with free electrons and positive ions
• In medicine, plasma refers to the use of ionized gases or partially ionized gases for therapeutic purposes
• Plasma medicine harnesses the unique properties of plasma, such as reactive species, charged particles, and electromagnetic fields, to interact with biological systems
• Medical applications of plasma include wound healing, sterilization, cancer treatment, and dental procedures
• Plasma devices used in medicine generate non-thermal plasma at or near room temperature allows for safe application on living tissues without causing thermal damage
• Plasma medicine is an interdisciplinary field combines physics, chemistry, biology, and medicine to develop novel therapeutic approaches
• The ability of plasma to selectively target and kill cancer cells while minimizing damage to healthy tissues makes it a promising tool in cancer therapy

Cancer Basics: A Quick Refresher

• Cancer is a group of diseases characterized by uncontrolled growth and spread of abnormal cells in the body
• Carcinogenesis, the process of cancer development, involves multiple stages: initiation, promotion, and progression
• Genetic mutations in oncogenes and tumor suppressor genes play a crucial role in cancer development
• Hallmarks of cancer include sustained proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis
• Tumors can be benign (non-cancerous) or malignant (cancerous) based on their ability to invade and spread to other parts of the body
• Cancer staging (TNM system) describes the extent of cancer in the body based on tumor size (T), lymph node involvement (N), and presence of metastasis (M)
• Treatment options for cancer include surgery, radiation therapy, chemotherapy, targeted therapy, and immunotherapy
  • Surgery aims to remove the tumor and surrounding affected tissues
  • Radiation therapy uses high-energy radiation to kill cancer cells and shrink tumors
  • Chemotherapy uses drugs to kill rapidly dividing cancer cells throughout the body
  • Targeted therapy focuses on specific molecules involved in cancer growth and progression
  • Immunotherapy harnesses the body's immune system to fight cancer cells

How Plasma Interacts with Cancer Cells

• Plasma generates reactive oxygen and nitrogen species (RONS) which can induce oxidative stress in cancer cells leading to cell death
• Charged particles in plasma can disrupt the cell membrane integrity of cancer cells causing membrane permeabilization and cell lysis
• Plasma-generated electromagnetic fields can affect cell signaling pathways involved in cancer cell survival and proliferation
• Plasma exposure can trigger apoptosis (programmed cell death) in cancer cells by activating caspase enzymes and inducing DNA damage
• Selective targeting of cancer cells by plasma is attributed to the higher sensitivity of cancer cells to oxidative stress compared to normal cells
  • Cancer cells have higher metabolic rates and lower antioxidant defenses making them more vulnerable to plasma-induced oxidative damage
• Plasma can enhance the immune response against cancer cells by stimulating the production of immunogenic cell death markers and activating immune cells
• Synergistic effects of plasma with conventional cancer therapies (chemotherapy and radiation) have been observed enhances treatment efficacy and reduces side effects

Types of Plasma-Based Cancer Treatments

• Plasma jet therapy uses a handheld device to generate a stream of plasma directed at the tumor site for localized treatment
  • Plasma jets can be used for superficial tumors (skin cancer) or in combination with minimally invasive surgical procedures for deep-seated tumors
• Plasma-activated medium (PAM) involves exposing a liquid medium (water or cell culture medium) to plasma generates RONS-rich solution with anticancer properties
  • PAM can be administered intravenously, intraperitoneally, or directly injected into the tumor site for systemic or localized treatment
• Plasma-activated saline (PAS) is a specific type of PAM prepared by exposing saline solution to plasma has shown promising results in cancer treatment
• Plasma-activated nanoparticles combine the benefits of plasma and nanotechnology for targeted delivery of anticancer agents to tumor sites
  • Plasma treatment can modify the surface properties of nanoparticles enhancing their stability, biocompatibility, and cellular uptake
• Plasma-based immunotherapy involves using plasma to stimulate the immune system and enhance the body's natural defense against cancer cells
  • Plasma can induce immunogenic cell death in cancer cells releasing tumor antigens and danger signals that activate immune responses

Key Benefits of Plasma in Cancer Therapy

• Selective targeting of cancer cells while minimizing damage to healthy tissues reduces side effects and improves patient quality of life
• Localized treatment with plasma devices allows for precise control over the treatment area minimizing systemic toxicity
• Plasma can penetrate deep into the tumor tissue reaching areas inaccessible to conventional therapies enhances treatment efficacy
• Synergistic effects of plasma with chemotherapy and radiation therapy can improve treatment outcomes and reduce the required doses of conventional therapies
• Plasma-based treatments have shown potential in overcoming drug resistance in cancer cells by inducing alternative cell death pathways
• Plasma can stimulate the immune system against cancer cells providing a long-lasting anti-tumor immune response
• Plasma treatments are generally well-tolerated by patients with minimal side effects compared to conventional cancer therapies
• The ability of plasma to induce apoptosis in cancer cells reduces the risk of secondary malignancies associated with necrotic cell death

Challenges and Limitations

• Standardization of plasma devices and treatment protocols is necessary to ensure consistent and reproducible results across different studies and clinical settings
• Long-term safety and efficacy of plasma-based cancer treatments need to be established through large-scale clinical trials
• Optimization of plasma parameters (gas composition, power, frequency, exposure time) for specific cancer types and stages is required to maximize treatment efficacy
• Penetration depth of plasma into tumor tissues can be limited in deep-seated tumors may require combination with other delivery methods (nanoparticles, PAM)
• Potential off-target effects of plasma on surrounding healthy tissues need to be carefully assessed and minimized
• Resistance mechanisms of cancer cells to plasma treatment are not fully understood may limit the long-term effectiveness of plasma therapy
• Cost and accessibility of plasma devices and treatments may be a barrier to widespread adoption in clinical settings
• Lack of awareness and understanding of plasma medicine among healthcare professionals and patients may hinder the integration of plasma-based therapies into standard cancer care

Current Research and Future Directions

• Elucidating the molecular mechanisms underlying the selective anticancer effects of plasma is crucial for optimizing treatment strategies
• Investigating the synergistic effects of plasma with other cancer therapies (immunotherapy, targeted therapy) can expand the therapeutic potential of plasma medicine
• Developing novel plasma devices with improved control over plasma parameters and delivery methods can enhance treatment precision and efficacy
• Exploring the use of plasma-activated liquids (PAM, PAS) as a systemic approach to cancer treatment can overcome the limitations of localized plasma application
• Studying the long-term effects of plasma treatment on cancer recurrence and metastasis can provide insights into the durability of plasma-induced anticancer responses
• Identifying biomarkers that predict the response to plasma treatment can enable personalized therapy and patient stratification
• Conducting large-scale, multicenter clinical trials to validate the safety and efficacy of plasma-based cancer treatments is essential for translation into clinical practice
• Investigating the potential of plasma in combination with cancer vaccines and adoptive cell therapies can enhance the specificity and potency of cancer immunotherapy

Real-World Applications and Case Studies

• Plasma jet therapy has been successfully used to treat superficial skin cancers (basal cell carcinoma, squamous cell carcinoma) with high response rates and minimal scarring
• Plasma-activated medium (PAM) has shown promising results in treating glioblastoma, an aggressive brain cancer, by inducing apoptosis and inhibiting tumor growth in preclinical models
• Plasma-activated saline (PAS) has been used as an adjuvant treatment for ovarian cancer in combination with chemotherapy resulting in improved survival and reduced tumor burden in animal studies
• Plasma-based immunotherapy has demonstrated potential in treating melanoma by inducing immunogenic cell death and stimulating anti-tumor immune responses in preclinical studies
• A clinical case report described the successful use of plasma jet therapy in treating a patient with advanced head and neck cancer resulting in significant tumor regression and improved quality of life
• Plasma-activated nanoparticles loaded with chemotherapeutic drugs have shown enhanced anticancer efficacy and reduced side effects in preclinical models of breast cancer and lung cancer
• A pilot clinical study investigated the use of plasma jet therapy for palliative treatment of advanced pancreatic cancer reporting improved pain control and quality of life in treated patients
• Plasma-activated medium has been explored as a potential treatment for colorectal cancer in combination with conventional chemotherapy showing synergistic effects and reduced drug resistance in preclinical studies