ArticleUltrasonics sonochemistry2026
Ultrasound-responsive nanodroplets activate the Hippo pathway via ROS-MST1-YAP cascade for breast cancer therapy.
Article in Ultrasonics sonochemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Dysregulated Hippo signaling critically promotes malignant proliferation, invasion and distant metastasis across multiple cancers, while precise and coordinated modulation of this core pathway remains a major unmet therapeutic hurdle in clinical cancer treatment. Here, we report for the first time the albumin-based, ultrasound-responsive nanodroplets (FLU-NDs) encapsulating fluvastatin (FLU) to achieve accurate and targeted Hippo pathway reprogramming for efficient tumor suppression. FLU-NDs possess satisfactory drug-loading capability, excellent biocompatibility, and robust contrast-enhanced ultrasound performance. Notably, FLU-NDs achieve efficient tumor accumulation through a dual-delivery strategy that integrates albumin-mediated enrichment with ultrasound-triggered spatiotemporal precise release. Mechanistically, we provide evidence for the first time that ultrasound-targeted microbubble destruction (UTMD) combined with FLU-NDs enables synergistic modulation of Hippo pathway through a reactive oxygen species (ROS)-mammalian sterile 20-like kinase 1 (MST1)-yes-associated protein (YAP) regulatory axis. Specifically, cavitation-induced ROS effectively activates upstream kinase MST1, while ultrasound-triggered release of FLU suppresses the downstream YAP, thereby facilitating coordinated upstream activation and downstream inhibition. Using this previously unrecognized UTMD-associated Hippo modulation strategy, FLU-NDs induce robust apoptosis, reverse EMT, and significantly inhibit tumor growth and metastasis in vitro and in vivo. Collectively, this study establishes a novel, high-efficacy and low-toxicity theranostic platform for precise Hippo-targeted cancer therapy.
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