All‐Flex Plasma Patch for In Vivo Delivery of Reactive Species

ABSTRACT Wearable cold atmospheric plasma (CAP) systems hold promise for oncology, but clinical translation has been hindered by limited flexibility, suboptimal skin contact, and insufficient mechanistic evidence. Here, we report an All‐Flex Plasma Patch (AFPP), a fully stretchable CAP platform capable of ambient‐air operation, designed for non‐invasive, safe, and effective cancer therapy. In a subcutaneous melanoma model, one‐week AFPP treatment drives pronounced tumor regression, achieving only 1/19 of the tumor volume observed in control group. The device demonstrates enhanced transdermal penetration of reactive oxygen and nitrogen species (RONS) compared with rigid plasma sources, indicating its potential as a cross‐barrier delivery system with excellent biocompatibility and minimal systemic burden. Moreover, we identify adverse responses under excessive exposure and outline an initial therapeutic range balancing efficacy and potential side effects, highlighting its low side effects under optimized conditions. Utilizing this platform, we systematically reveal that AFPP treatment regulates multiple previously unreported key proteins, drives metabolic reprogramming and disrupts calcium homeostasis, and it inhibits tumor progression by orchestrating multiple cell death modalities. This work provides preliminary mechanistic insights supporting the development of safe and effective wearable CAP therapy, and outlines a framework relevant to the translational advancement of non‐invasive plasma oncology as a complement to conventional treatments.