Cerebral ischemic area is considered to be an acidic pathological tissue due to the accumulation of lactic acid by the high rate of glycolysis. As a result, this acidic tissue environment provides an opportunity which has been applied for specific targeting diagnosis. Therefore, the design of pH-triggerable targeting imaging probes for the detection of cerebral ischemic area has attracted more attention for the prediction of stroke. A smart nanoparticle was constructed through self-assembly of Fe3O4 nanoparticles and pH-responsive mPEG-b-P(DPA-DE)LG copolymer, which could maintain the stabilized core-shell structure state at physiological pH, whereas Fe3O4 nanoparticles can be released in response to low pH environment. Moreover, this intelligent nanoparticle also showed biocompatibility, T2-weighted contrast-enhancement ability, low toxicity, and long-term stability. A rat bearing cerebral ischemia disease were used to evaluate the effectiveness of Fe3O4-loaded mPEG-b-P(DPA-DE)LG as acidic pH-triggerable targeting MRI probes. The in vivo MRI results confirmed that a gradual change in contrast in the cerebral ischemic area could be visualized by MRI after 1 hour, and maximal signal loss was detected after 24 h post-injection. Therefore, the team believed that Fe3O4-loaded mPEG-b-P(DPA-DE)LG with unique acid-triggered abilities may have more generalized applications in biomedical diagnostic due to their ability to target other acidic pathologic tissues. This research was published in the journal Nanoscale of Royal Society of Chemistry, UK.