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However, wirelessly controlling drug release from implanted devices via exogenous stimulation remains challenging. Herein, an ultrasound wirelessly controlled electrically responsive implantable drug delivery system (UI\u2010TENG\u2010IDDS) is proposed, which consists of an ultrasound\u2010driven implantable triboelectric nanogenerator (UI\u2010TENG) and an electrically responsive drug reservoir. When ultrasound is applied to the skin, it induces high\u2010frequency vibrations in the UI\u2010TENG, generating pulsed electrical output (\u224850\u00a0\u00b5A at 9\u00a0V) to electrolyze water, thereby increasing the alkalinity near the cathode and dissolving drug carrier (co\u2010PMMA) to release drugs. Moreover, UI\u2010TENG\u2010IDDS can accelerate the diffusion of negatively charged drugs via iontophoresis mechanism. Methotrexate (MTX) loaded UI\u2010TENG\u2010IDDS has been applied to ablate tumors without causing evident side effects. The UI\u2010TENG\u2010IDDS can wirelessly control drug release without complex electronic design and the electrical outputs are not limited by the battery life and capacity, avoiding battery replacement surgery. Considering the advantage that TENG can be fabricated using biodegradable and biocompatible materials, this work provides an efficient, economical, and safe regimen for spatiotemporal controlled implantable drug delivery.<\/jats:p>","DOI":"10.1002\/smll.202412704","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T08:25:31Z","timestamp":1750148731000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ultrasound Wirelessly Controlled Electrically Responsive Implantable Drug Delivery System for Enhanced Tumor Therapy"],"prefix":"10.1002","volume":"21","author":[{"given":"Haimei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopedics Trauma and Microsurgery Zhongnan Hospital of Wuhan University School of Pharmaceutical Sciences Wuhan University  Wuhan 430071 China"},{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE) Wuhan University  Wuhan 430072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangqin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Trauma and Microsurgery Zhongnan Hospital of Wuhan University School of Pharmaceutical Sciences Wuhan University  Wuhan 430071 China"},{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE) Wuhan University  Wuhan 430072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Trauma and Microsurgery Zhongnan Hospital of Wuhan University School of Pharmaceutical Sciences Wuhan University  Wuhan 430071 China"},{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE) Wuhan University  Wuhan 430072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyu","family":"Li","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Nanomedicine College of Life Science and Technology Huazhong University of Science and Technology  Wuhan 430074 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hu","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Nanomedicine College of Life Science and Technology Huazhong University of Science and Technology  Wuhan 430074 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7380-593X","authenticated-orcid":false,"given":"Peng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Trauma and Microsurgery Zhongnan Hospital of Wuhan University School of Pharmaceutical Sciences Wuhan University  Wuhan 430071 China"},{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE) Wuhan University  Wuhan 430072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201706665"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.01.018"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.10.046"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.06.010"},{"key":"e_1_2_8_4_2","volume":"483","author":"Sun P.","year":"2024","journal-title":"Chem. 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