tPA-DPN did not increaselesion volume or BBB permeability, unlike free-tPA, which led to anover 2-fold enlarged lesion volume and 50% higher BBB permeability.The safety profile of tPA-DPN is attributed to the robust conjugationof tPA onto DPN and the lack of DPN extravasation, resulting in negligiblecerebrovascular damage of free tPA and glial and neuron impairment.The vascular confinement of tPA linked to microscopic particles reducesdrug side effects and represents a valuable strategy for safe andeffective tPA delivery, even in the postacute stroke phase. Here, PLAT is linked to Stroke.