Background <p>Stroke is a class of acute cerebrovascular diseases, among which ischaemic stroke is characterized by high morbidity and high recurrence rate. Due to multiple pathological mechanisms, it is very easy to cause cerebral ischaemia-reperfusion injury (RI). To quickly and effectively regulate the complex and variable cerebral immune microenvironment (IM) and reduce RI, the study aims to use a versatile immunosuppressive nanosystem (VIN) to efficiently remodel the overactivated brain IM and alleviate RI, thereby enhancing the effects of ischemic stroke (IS). Methods: The study first induced high expression of CXCR4 receptor in rat bone marrow mesenchymal stem cell membranes using Fe₃O₄ nanoparticles, then extracted the cell membranes by hypotonic lysis and repeated freeze-thawing and reconstituted using ultrasound to form engineered bionic decoy vesicles. Next, polydopamine nanoparticles were prepared by oxidative self-polymerization, using Zn²⁺ as a bridge to obtain A151-loaded polydopamine nanoparticles. Finally, it was reconstituted with engineered bionic decoy vesicles using ultrasonic cavitation to prepare a VIN integrated with engineered bionic decoys. Results: It was shown that Fe₃O₄ nanoparticles (Fe₃O₄ NPs) could significantly increase the expression level of CXCR4 receptor. In rats treated by the VIN group, the body weight had increased to near the normal level by day 7, and the infarct area was reduced by 89.4%. The results showed that VIN was able to effectively reduce the volume of cerebral ischemic infarction in rats in long-term treatment, and had a good therapeutic effect on IS. Conclusion: The study achieved internal and external synergistic immunosuppressive effects to effectively and safely regulate the excessive IM after reperfusion, which provides a new idea to alleviate ischaemia-RI.</p> <p></p>