Nitric oxide-functionalized 2D metal-organic framework nanosheets for ultrasound-induced synergistic gas/sonodynamic cancer therapy

Sonodynamic therapy (SDT) has garnered significant attention due to its deep tissue penetration and biocompatibility. Nevertheless, the therapeutic outcomes of conventional SDT are substantially constrained by tumor hypoxia and the transient lifespan of reactive oxygen species (ROS). Herein, we report the nitric oxide (NO)-functionalized two-dimensional (2D) metal-organic framework (MOF) nanosheets as an efficient nanoplatform for ultrasound (US)-induced synergistic gas/sonodynamic cancer therapy. Zinc ions are initially chelated at the porphyrin center within the MOF framework (In-TCPP), followed by successive coordination and adsorption of NO gas to yield the NO-functionalized MOF (In-TCPP@Zn–NO). In comparison to pristine In-TCPP nanosheets, the US treatment can not only induce the efficient ROS generation but also trigger the efficient and rapid release of NO gas from the In-TCPP@Zn–NO nanosheets. Importantly, while maintaining comparable SDT efficacy to pristine In-TCPP nanosheets, the In-TCPP@Zn–NO demonstrates US-responsive NO release behavior with enhanced kinetics and distinct temporal regulation characteristics. Therefore, both in vitro and in vivo results demonstrate that US triggers the synergistic enhancement of SDT effectiveness by ROS generation and NO release from In-TCPP@Zn–NO nanosheets, leading to the eradication of cancer cells and tumors. © 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.