Focused ultrasound for cellular mechanoactivation and nanomedicine delivery in cancer

Focused ultrasound (FUS) generates acoustic forces that activate cellular mechanotransduction, including calcium signaling via mechanosensitive ion channels, and modulates nanoparticle behavior through physical and chemical perturbations. These coupled effects have been leveraged to enhance anti-cancer drug delivery and reshape tumor transport dynamics. Integration of FUS with nanodrug systems enables coordinated modulation of vascular permeability, intratumoral distribution, and tumor microenvironment (TME) remodeling. Advanced cancer-on-a-chip platforms provide physiologically relevant in vitro models for systematically evaluating these multiscale interactions under controlled conditions. Together, these elements form an integrated framework linking FUS-induced physicochemical mechanisms to biological responses, nanoparticle behavior, and chip-based evaluation. This review presents the biological and transport-associated roles of FUS in cancer therapy, discusses its integration with nanodrug systems to modulate TME dynamics, and highlights the application of cancer-on-a-chip technologies to assess FUS-mediated transport modulation and nanodrug performance in preclinical settings.