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Using in vivo measurements and computational modelling it is shown that LMCs experience elevated fluid shear stress that is significantly higher than that in other blood vessels during ischaemic stroke in rats and humans. We exploit this to selectively enhance flow in LMCs using shear\u2010activated nanoparticle aggregates carrying the vasodilator nitroglycerin (NG\u2010NPAs) that specifically release drug in regions of vessels with high wall shear stress (\u2265100 dyne\u00a0cm\n                    <jats:sup>\u22122<\/jats:sup>\n                    ). NG\u2010NPAs significantly increased LMC\u2010mediated penumbral perfusion, decreased infarct volume, and reduced neurological deficit without altering systemic blood pressure in a rat ischaemic stroke model. NG\u2010NPAs also avoided common side effects of systemic nitrate administration, such as systemic hypotension, cerebral vascular steal, cortical vein dilation, or intracranial pressure elevation. Systemic administration of free NG at the maximal tolerated dose, which is ten times higher than the dose of NG used in the NG\u2010NPAs, do not enhance LMC perfusion and dropped blood pressure. Thus, packaging NG within shear\u2010activated NPAs can potentially enable this widely available vasodilator to become a highly effective therapeutic for ischaemic stroke.\n                  <\/jats:p>","DOI":"10.1002\/advs.202506276","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T08:11:37Z","timestamp":1755072697000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Shear Stress Targeted Delivery of Nitroglycerin to Brain Collaterals Improves Ischaemic Stroke Outcome"],"prefix":"10.1002","volume":"12","author":[{"given":"Magdalena","family":"Litman","sequence":"first","affiliation":[{"name":"School of Biomedical Science and Pharmacy The University of Newcastle  Newcastle 2308 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Azarpeykan","sequence":"additional","affiliation":[{"name":"School of Biomedical Science and Pharmacy The 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