Development and assessment of a reactive oxygen species generator independent of external stimuli utilizing metal–organic frameworks

Our research showed that the nanoparticles incorporated within the Metal-Organic Framework (MOF) substrate can facilitate self-driven electron transfer without the need for external stimulation to produce reactive oxygen species (ROS). The potential difference between bismuth nanoparticles and the central metal in the MOF is recognized as a key factor in the process of autonomous electron transfer. This study investigates the impact of central metal on electrochemical performance of bismuth nanoparticles and the production of active radical species. In this work, the MOF-303 with aluminum central metal was chosen to reduce the potential difference compared to previous our research focused on zirconium metal. The results indicate that the reduction in potential difference leads to a decrease in impedance and an increase in semiconductor capability. These changes improve the performance of bismuth nanoparticles in electron transfer, resulting in increased production of reactive oxygen species (ROS) under physiological conditions. Concurrently, this system depletes intracellular glutathione (GSH), converting it to oxidized glutathione (GSSG), and thereby disrupts redox homeostasis in tumor microenvironments. The acidic pH further enhances GSH oxidation, demonstrating the potential of Bi@MOF-303 as a pH-responsive, self-driven ROS amplifier. Live/dead cell staining assay validated the findings, revealing that Bi@MOF-303 had the highest percentage of cell death. This was due to significant oxidative stress caused by its self-driven electron transfer and depletion of GSH. Our innovative protocol, which emphasizes the accumulation of ROS in cancer cells through self-driven electron transfer, highlights the importance of central metal selection and its impact on electrical behavior and active species production for the first time.