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The majority of endocytosed nanoparticles are degraded before nucleic acid release, and an inability to track particle distribution\n                  <jats:italic>in vivo<\/jats:italic>\n                  prevents validation of successful delivery. Alternatively, nanobubbles (NBs) are lipid-shelled, gas-core preclinical ultrasound contrast agents and stimuli-responsive drug delivery vehicles. Under varying acoustic pressures, NBs expand, contract, and burst, releasing cargo in an externally controlled, site-specific manner while scattering unique echoes for simultaneous ultrasound visualization. Here, we introduce a cationic nanobubble (CNB) formulation with a +42.3 mV zeta potential, 265 nm diameter, and 2.43\u00d710\n                  <jats:sup>11<\/jats:sup>\n                  NBs\/mL concentration. CNBs produce stable ultrasound contrast, electrostatically load plasmid DNA onto their surface, and internalize into &gt;99% of human prostate cancer cells within 15 minutes\n                  <jats:italic>in vitro.<\/jats:italic>\n                  CNBs remain brightly echogenic intracellularly and induce sonication-dependent expression of green fluorescent protein (GFP).\n                  <jats:italic>In vivo<\/jats:italic>\n                  , CNBs generate contrast in mouse livers for 50 minutes after intravenous administration. Therapeutic ultrasound stimulation over the liver causes a sharp reduction in ultrasound contrast, visualizing localized cavitation in the target organ and inducing a 2.5-fold increase in anti-GFP mean fluorescence intensity relative to the untransfected control. Importantly, no GFP expression is observed without ultrasound stimulation, supporting a mechanism for selective and site-specific gene delivery. This study presents a highly stable CNB capable of efficient DNA loading and ultrasound-dependent gene expression. These results provide a foundation for the future development of CNB platforms to advance image-guided, ultrasound-triggered gene therapy.\n                <\/jats:p>","DOI":"10.64898\/2026.09.11.749060","type":"posted-content","created":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T13:25:11Z","timestamp":1789305911000},"source":"Crossref","is-referenced-by-count":0,"title":["Nonviral, ultrasound-triggered gene delivery platform via gas-core cationic nanobubbles"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6083-1338","authenticated-orcid":false,"given":"Laura E.","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1114-4328","authenticated-orcid":false,"given":"Pinunta","family":"Nittayacharn","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Phutthamonthon, Nakhon Pathom, Thailand"},{"name":"Department of Radiology, Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-4070","authenticated-orcid":false,"given":"Aayushi","family":"Laliwala","sequence":"additional","affiliation":[{"name":"Department of Radiology, Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus Vincent","family":"Bella Jaro","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9695-2529","authenticated-orcid":false,"given":"Salima","family":"El Yakhlifi","sequence":"additional","affiliation":[{"name":"Department of Radiology, Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean F.","family":"Eastman","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1977-1046","authenticated-orcid":false,"given":"Xu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6591-0564","authenticated-orcid":false,"given":"Aaqib H.","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Radiology, Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"HartMoore","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, The University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0632-3719","authenticated-orcid":false,"given":"Fatma","family":"Dogan","sequence":"additional","affiliation":[{"name":"Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina F.","family":"Giai","sequence":"additional","affiliation":[{"name":"Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Brauns","sequence":"additional","affiliation":[{"name":"Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Poznansky","sequence":"additional","affiliation":[{"name":"Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5063-6096","authenticated-orcid":false,"given":"Richard K.P.","family":"Benninger","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, The University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2602-023X","authenticated-orcid":false,"given":"Marvin T.","family":"Nieman","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences, Case Western Reserve University, 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