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We developed electrical BBB modulation (eBBB), an on-demand platform combining vascular-targeting poly-L-lactic acid nanoparticles with high-definition transcranial direct current stimulation to achieve spatially and temporally controlled BBB opening. eBBB produced localized, reversible increases in BBB permeability confined to the stimulated cortex, with the opening area tunable via electrode geometry. This transient window enhanced regional delivery of a small-molecule drug, full-length immunoglobulins, and adeno-associated viral vectors, which are cargo classes otherwise completely excluded by the intact BBB. Neurovascular unit architecture was preserved with no lasting histological damage. Integrating a biodegradable nanomaterial with a clinically evaluated stimulation technology, eBBB offers a programmable, minimally invasive strategy for regional CNS drug delivery across brain malignancies and neurological disorders.<\/jats:p>\n                <jats:sec>\n                  <jats:title>One sentence summary<\/jats:title>\n                  <jats:p>Electrical activation of piezoelectric nanoparticles reversibly opens the blood-brain barrier for minimally invasive drug delivery to targeted cortical regions.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.20.738792","type":"posted-content","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:15:22Z","timestamp":1784715322000},"source":"Crossref","is-referenced-by-count":0,"title":["On-demand, reversible blood-brain barrier opening via electrical activation of piezoelectric nanoparticles for targeted brain drug delivery"],"prefix":"10.64898","author":[{"given":"Salona","family":"Roy","sequence":"first","affiliation":[{"name":"Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umisha","family":"Siwakoti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Louisiana Tech University, Ruston, LA 71272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Alday","sequence":"additional","affiliation":[{"name":"Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Astete","sequence":"additional","affiliation":[{"name":"Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"McElveen","sequence":"additional","affiliation":[{"name":"Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Sigdel","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Louisiana Tech University, Ruston, LA 71272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Del Piero","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Sabliov","sequence":"additional","affiliation":[{"name":"Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Castagnola","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Louisiana Tech University, Ruston, LA 71272, USA"},{"name":"Institute for Micromanufacturing, Louisiana Tech University, Ruston, LA 71272, USA"},{"name":"Department of Neurosurgery, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4820-805X","authenticated-orcid":false,"given":"Qi","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072408200934000_2026.07.20.738792v1.1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020412"},{"key":"2026072408200934000_2026.07.20.738792v1.2","doi-asserted-by":"publisher","DOI":"10.1186\/2045--8118--9--23"},{"key":"2026072408200934000_2026.07.20.738792v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4288"},{"key":"2026072408200934000_2026.07.20.738792v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1824"},{"key":"2026072408200934000_2026.07.20.738792v1.5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03696.x"},{"key":"2026072408200934000_2026.07.20.738792v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.07.030"},{"key":"2026072408200934000_2026.07.20.738792v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2015.08.003"},{"key":"2026072408200934000_2026.07.20.738792v1.8","doi-asserted-by":"crossref","unstructured":"J. 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