Cold atmospheric plasma for gas therapy and gas-activated drug delivery

Cold atmospheric plasma (CAP) has emerged as a promising tool for in situ gas delivery due to its ability to generate reactive oxygen and nitrogen species, which play a crucial role in oxidative stress-mediated therapeutic effects. As the fourth state of matter, CAP is characterized by unique physicochemical properties and distinct generation mechanisms, which are discussed in terms of its fundamental principles and production techniques. This review covers current CAP delivery methods, highlighting their critical role in biomedical applications. The diverse therapeutic potential of CAP is explored, including its immunomodulatory effects in cancer therapy and its antimicrobial properties in wound healing through generation of reactive oxygen and nitrogen species. CAP also demonstrates efficacy in oral, inflammatory, gastrointestinal, and neurological conditions by eliminating biofilms, promoting tissue regeneration, and modulating immune and intracellular redox signaling pathways. Additionally, special emphasis is placed on the synergistic integration of CAP with advanced drug delivery systems to enhance therapeutic efficacy. Current challenges, potential limitations, and future directions for CAP-based biomedical applications are addressed. Despite its significant potential, challenges such as precise dose control, biological safety, and clinical translation remain unresolved. Future research should focus on optimizing CAP-based therapies, developing targeted delivery strategies, and conducting comprehensive clinical studies to facilitate its integration into mainstream medical practice.