[Synergistic regulation of neuro-tumor interactions by ultrasound and biomaterials]

The peripheral nervous system plays an important role in remodeling the tumor microenvironment (TME) and promoting malignant progression through the release of neurotransmitters and neuropeptides, regulation of immune cell function, and remodeling of the neural microenvironment. However, conventional strategies such as surgical denervation and pharmacological blockade are limited by poor specificity, irreversible injury, and systemic adverse effects. Ultrasound neuromodulation, as a noninvasive and controllable physical intervention, provides a novel technical approach for the dynamic regulation of peripheral nerve activity. This review first systematically summarizes the functional mechanisms by which autonomic nerves, sensory nerves, and Schwann cells (SCs) regulate tumors, and then describes how low-intensity pulsed ultrasound (LIPUS) and low-intensity focused ultrasound (LIFU) remodel the TME by modulating ion channel activity, neurotransmitter release, and SC plasticity. Recent advances in ultrasound-responsive piezoelectric nanomaterials and molecular delivery systems are further discussed, including strategies to enhance acoustic signal transduction, enable controlled release of neuroactive molecules, and improve the precision of neuromodulation. Ultrasound neuromodulation can effectively modulate peripheral nerve function, and its integration with ultrasound-responsive biomaterials may enhance targeting precision, demonstrating potential for application in cancer therapy.