Unveiling the interface effects of plasma-activated micro-nano bubbles water: An emerging avenue for cancer therapy

Plasma-activated water (PAW) is widely recognized as a promising anticancer agent owing to its abundance of reactive oxygen and nitrogen species (RONS), which selectively target cancer cells. However, the clinical translation of PAW has been hindered by the relatively low concentration and short half-lives of its RONS components. Herein, this Letter proposes a promising strategy for cancer therapy via utilizing plasma-activated micro-nano bubbles water (MNBs-PAW). Compared with conventional PAW, MNBs-PAW exhibits significantly enhanced concentrations and prolonged half-lives of aqueous RONS. Notably, while the H₂O₂ concentration shows a slight decrease, the levels of NO₂⁻, ONOO⁻/O₂⁻, OH, and ¹O₂ are substantially elevated. Furthermore, the half-lives of short-lived species (ONOO⁻/O₂⁻, OH, and ¹O₂) are extended by factors of 4, 4, and 2, respectively. These improvements are attributed to the introduced micro-nano bubbles enhancing the gas–liquid mass transfer efficiency of gaseous RONS and prolonging the residence time of aqueous RONS through their unique interface effects. The elevated RONS levels and their synergistic redox reactions induce a significant accumulation of intracellular ROS levels within A549 cancer cells (predominantly O₂⁻ and OH), indicating that MNBs-PAW possesses substantially superior anticancer efficacy to conventional PAW. This study not only introduces an innovative approach for PAW preparation but also highlights a promising direction for clinical cancer therapy.