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Despite advances in treatment, poor drug penetration and uncontrolled release continue to impede the effectiveness of chemotherapy for this disease. To overcome these obstacles, we have developed a self-driven electrical triggering system, which leverages intravesical pressure to produce electricity. This electronic trigger system can rapidly transport hydroxycamptothecin through tunneling nanotubes, acting as a high-speed channel, thereby enhancing the drug absorption by tumor cells. Additionally, the voltage generated by this system effectively induces reactive oxygen species (ROS), further promoting the eradication of bladder cancer cells. In orthotopic female animal models of bladder cancer, our results indicate that an intravesical pressure-driven system in the bladder generates electricity to facilitate drug release and rapid diffusion through a tunneling nanotube highway, while also effectively generating ROS to eliminate bladder cancer cells. This self-driven electrical trigger system, coupled with a tunneling nanotube highway to transport drugs, offers renewed hope for bladder cancer treatment. With its potential to transform current therapeutic approaches, this system is poised for deeper exploration in research and clinical settings.<\/jats:p>","DOI":"10.1038\/s41467-025-65017-2","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T12:52:55Z","timestamp":1763470375000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Self-driven electrical triggering system activates tunneling nanotube highways to enhance drug delivery in bladder cancer therapy"],"prefix":"10.1038","volume":"16","author":[{"given":"Zhijun","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0077-1513","authenticated-orcid":false,"given":"Ravindra","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongguo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0072-0847","authenticated-orcid":false,"given":"Fulin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuxiu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1793-7858","authenticated-orcid":false,"given":"Zong-Hong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7705-8567","authenticated-orcid":false,"given":"Yang-Bao","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"65017_CR1","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/s41571-023-00744-3","volume":"20","author":"LM van Hoogstraten","year":"2023","unstructured":"van Hoogstraten, L. 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