Nanomedicine-based therapeutic strategies for cerebral ischemia–reperfusion injury: from blood–brain barrier penetration to precision targeting

Cerebral ischemia-reperfusion injury (CIRI) represents a major contributing factor to adverse outcomes following ischemic stroke (IS), posing significant challenges to patient survival and long-term quality of life. Although various anti-inflammatory and antioxidant agents are currently employed clinically for CIRI treatment, their therapeutic efficacy remains constrained by blood-brain barrier (BBB) limitations and inherent drug limitations, including poor pharmacokinetics and limited in vivo stability. In recent years, nanotechnology has gained increasing prominence in the medical field, with rationally designed nanomedicines demonstrating enhanced BBB permeability and improved bioavailability, emerging as a promising therapeutic approach for CIRI. This review provides a concise overview of the pathological mechanisms underlying CIRI, highlights recent advances in various nanomedicines carrier systems, explores multiple delivery strategies ranging from passive diffusion to active targeting across the BBB, and discusses cutting-edge therapeutic approaches for precision targeting of specific organelles and cellular compartments, with the aim of providing novel insights for subsequent CIRI delivery strategies and therapeutic targets.