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Current treatments primarily rely on thrombolytic agents like alteplase, urokinase, and streptokinase for rapid reperfusion. However, these therapies are limited by narrow therapeutic windows, rapid clearance, poor blood\u2010brain barrier (BBB) penetration, off\u2010target effects, and the complex ischemic microenvironment. These have led to increased interest in nanomaterial\u2010based platforms to improve the precision and efficacy of IS treatment. The IS microenvironment, characterized by oxidative stress, inflammation, ionic imbalance, acidosis, and BBB disruption, provides valuable cues for designing responsive nanomaterials. Nanomaterials engineered to respond to reactive oxygen species, pH, enzymes, light, ultrasound, or magnetic fields can enable targeted drug delivery, controlled release, and multi\u2010modal interventions, enhancing therapeutic precision. 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