Pathogenesis-adaptive polydopamine nanosystem for sequential therapy of ischemic stroke

Abstract Ischemic stroke is lethal cerebrovascular disease, and reperfusion as the main strategy of blood supply restoration can cause severe ischemic brain damage. Considered as the major obstacle in medication for stroke, neuroinflammation after reperfusion undergoes dynamic progression, making precision treatment for stroke a Herculean task. In this work, we report a pathogenesis-adaptive polydopamine nanosystem for sequential therapy of ischemic stroke. Intrinsic free radical scavenging and tailored mesostructure of the nanosystem can attenuate oxidative stress at the initial stage. Upon microglial overactivation at the later stage, minocycline-loaded nanosystem can timely reverse the pro-inflammatory transition in response to activated matrix metalloproteinase-2, providing on-demand regulation. Further in vivo stroke study demonstrates a higher survival rate and improved brain recovery of the sequential strategy, compared with mono-therapy and combined therapy. Complemented with satisfactory biosafety results, this adaptive nanosystem for sequential and on-demand regulation of post-stroke neuroinflammation is a promising approach to ischemic stroke therapy.