Imaging Guided Endogenic H 2 -Augmented Electrochemo-Sonodynamic Domino Cotherapy of Tumor in Vivo.

Precise and on-demand release of sufficient hydrogen (H 2 ) to the tumor sites remains a key challenge for emerging H 2 -oncotherapy, and little is known about the physiological effects of "abundant" H 2 on complex tumor microenvironments (TME). Here, we report a highly efficient and cost-effective imaging-guided/-assessed H 2 -therapy of tumors based on a joint electrochemo-sonodynamic treatment (H 2 -EC/SD cotherapy) with strong "domino effect" triggered by endogenous H 2 generation at tumor sites to speedily eliminate tumor tissue (≤80 mm 3 ) within 1 day. Adequate H 2 was controllably generated in tumor sites through mild electrochemistry in vivo due to acidic TME, by using clinic acupuncture Fe needle as electrodes. Besides starvation damage due to gas blockage destruction for vessels, nano-/micro-bubbles of H 2 formed in-situ can elevate its internal temperature and burst vessels to further destroy tumor under ultrasound irradiation. Remarkably, vulnerable homeostasis of TME was disturbed as H 2 also participates in physiological activity of tumor cells, leading to the tumor dysfunction. Last but not least, the inflammatory response of body from cancer was reduced after the treatment, beneficial for the body's immune system for post-treatment recovery. Based on all these merits, the H 2 -EC/SD cotherapy provides a potentially safe and viable therapeutic strategy for future clinical applications. This article is protected by copyright. All rights reserved.