Ultrasound-responsive micro/nanobubbles based intelligent theranostic systems for precision tumor therapy

Ultrasound-targeted micro/nanobubble cavitation (UTMC/UTNC) has emerged as a highly promising ultrasound-based strategy for precision tumor therapy. This technique harnesses microbubbles and nanobubbles as cavitation nuclei that respond to ultrasound, inducing cavitation effects, generating mechanical forces that transiently permeabilize biological barriers, enhance vascular and cellular permeability, and induce localized tumor cell disruption. These cavitation-mediated effects enable spatiotemporally controlled drug release, markedly improving intratumoral drug accumulation and maximizing therapeutic efficacy while reducing systemic toxicity. This review provides a comprehensive overview of the mechanistic foundations and therapeutic applications of UTMC/UTNC. The physical mechanisms by which bubbles act as cavitation nuclei, undergoing oscillation, expansion, collapse, or rupture under ultrasound stimulation, and their resulting biological effects are discussed in detail. Furthermore, emphasizing the roles of UTMC/UTNC in enhancing chemotherapy, sonodynamic therapy, immunotherapy, gene delivery, radiotherapy, and ferroptosis is reviewed. These therapeutic enhancements are primarily attributed to improved drug delivery and cavitation-induced tumor cell disruption. Finally, key challenges and limitations associated with UTMC/UTNC-mediated tumor therapy are discussed, along with prospects for clinical translation.