摘要
Purpose Precise control over the anatomical target and applied dosage with imaging guidance remains a major challenge in treating focal neurological disorders such as epilepsy. Here, we present a blood-brain barrier (BBB)-sparing, ultrasound (US)-responsive theranostic nanoplatform using phase-change propofol-loaded nanodroplets (Pro-NDs) that enables real-time monitoring of drug release for focal seizure suppression via US imaging.Methods Pro-NDs were fabricated by conjugating propofol-loaded liposomes onto microbubbles and recondensing them into liquid-core nanodroplets. Focused ultrasound (FUS) was applied to induce a pressure-dependent phase transition, triggering concurrent drug release and US contrast enhancement. The system was validated through in vitro correlation analyses and in vivo evaluations using epileptic rat models monitored by US imaging, electrocorticography (ECoG) spike activity, and histological analyses.Results The Pro-NDs (605.3 +/- 82.7 nm) achieved a drug-loading capacity of 95.2 +/- 1.0 & micro;g/mL. In vitro analyses revealed a strong correlation between contrast enhancement and drug release (R 2 = 0.99). In epileptic rats, FUS triggered focal contrast enhancement within the hippocampus and significantly suppressed spike activity in a pressure-dependent manner. An FUS pressure of 2.5 MPa achieved a maximum spike reduction of 59.4 +/- 12.3%, with therapeutic efficacy strongly correlating with US contrast (R 2 = 0.96). No detectable Evans blue extravasation or overt histological tissue injury was observed under the evaluated conditions.Conclusion The Pro-NDs-FUS system establishes a noninvasive, safe, imaging-guided theranostic platform for precision neurology, enabling effective seizure suppression while maintaining cerebrovascular integrity.