Real-time ROS monitoring-guided tumor electrodynamic therapy using a metal microneedle array system

Abstract

Currently, various strategies are employed to utilize reactive oxygen species (ROS) amplifiers in tumor therapy; Electrodynamic therapy (EDT) presents a promising modality for ROS amplification, as it can continuously produce substantial quantities of ROS independent of endogenous sources, thereby demonstrating potential antitumor activity. Nonetheless, achieving prolonged tumor suppression with EDT remains a significant challenge. Conventional EDT approaches frequently encounter issues with inadequate overlap between the active electric field region and the drug distribution area, resulting in insufficient electrocatalytic action and uneven ROS distribution. Furthermore, individual physiological variability can lead to disparate therapeutic outcomes from identical drug dosages, and indiscriminate increases in ROS dosage may inadvertently exacerbate tumor invasion and metastasis. To address these challenges, we developed a microneedle (MN) array system that combines ROS sensing and enables precise EDT therapy. The integrated system offers multifunctional capabilities, including drug delivery, electrical stimulation, and real-time ROS sensing. Benefiting from the homogeneously distributed electric field provided by the MN array, we significantly enhanced the electrocatalytic performance of electrodynamic nanomedicines. The integrated system produces cell-toxic ROS at 2.4 times the rate of traditional methods and induces tumor cell apoptosis 2.6 times more effectively. Real-time ROS monitoring via sensing electrodes allows precise drug dosage adjustments, ensuring effective ROS amplification therapy while minimizing waste. Adding DON further boosts ROS accumulation and strengthens anti-tumor immunity. The miniaturized dual-power supply strategy, combining a constant current source with ROS signal collection, enhances clinical suitability, optimizing both therapeutic efficacy and precision in tumor treatment.