Overcoming Biological Barriers with Sononanomedicine: New Horizons in Oncology and Neurology

Abstract Biological barriers, including the tumor microenvironment and the blood–brain barrier, represent the primary bottleneck for the clinical translation of nanomedicines in oncology and neurology. Ultrasound, characterized by noninvasiveness, deep tissue penetration, and high spatiotemporal precision, provides a transformative platform to address this challenge. This review systematically presents sononanomedicine as an integrated paradigm that couples acoustic physics with nanoplatform engineering to overcome these physiological barriers. We delineate the core physical mechanisms─cavitation, sonochemical effects, and thermal modulation─and highlight major classes of sononanomedicines. In oncology, we discuss ultrasound-assisted chemotherapy, sonodynamic and photothermal combination therapy, high intensity focused ultrasound (HIFU) ablation sensitization, and synergy with immunotherapy. For neurological disorders, we cover brain tumor therapy, neurodegenerative disease intervention, and spinal cord injury repair. Finally, we identify critical translational hurdles and propose that next-generation sononanomedicine must shift from platform-centric verification toward patient-centered optimization, integrating feedback-guided design and multimodal imaging to achieve reproducible and clinically viable therapeutic outcomes.