Perfluorocarbon nanotechnologies for blood-brain barrier modulation: Enhancing drug delivery and neuroprotection

The blood-brain barrier (BBB) presents a major obstacle to effective drug delivery for neurological disorders. Recent advances in perfluorocarbon (PFC) nanotechnologies have shown promise in modulating BBB permeability for improved therapeutic outcomes. This review explores the dual role of PFC-based systems in both enhancing drug delivery and stabilizing the BBB under pathological conditions. Unlike previous reviews that mainly emphasize microbubble-assisted focused ultrasound for BBB opening, this work specifically highlights the unique contributions of PFC nanotechnologies, including their laser- and ultrasound-responsiveness, smaller nanoscale formulations enabling deeper penetration, and their emerging neuroprotective properties. The use of PFC nanoemulsions combined with focused ultrasound (FUS) has demonstrated efficient cellular uptake and targeted drug delivery to brain tumors, while laser-activated PFC nanodroplets and low-boiling-point PFC nanodroplets offer transient BBB disruption via phase transitions and acoustic cavitation. Moreover, PFC derivatives like perfluorooctyl bromide (PFOB) have shown protective effects in models of subarachnoid hemorrhage by reducing BBB permeability and mitigating neuronal apoptosis. Despite these promising findings, challenges remain in optimizing PFC formulations, evaluating long-term safety, and understanding their mechanistic effects on the BBB. Future research should focus on refining these systems through combination strategies and exploring their potential in the treatment of neurodegenerative diseases and cerebrovascular disorders.