Perspectives and trends in gas delivery systems based on ultrasound responsive nanomaterials for cancer therapy

Gas-based therapeutic strategies (e.g., nitric oxide and carbon dioxide delivery) have shown promising potential for modulating the tumor microenvironment and enhancing anticancer efficacy. However, their clinical translation is limited by their poor spatiotemporal control, systemic toxicity, and limited tumor selectivity. As a powerful alternative, nanomaterial-based gas delivery systems offer improved stability, targeted accumulation, and programmable release in response to tumor-specific stimuli. Among various triggering methods, ultrasound has received particular attention because of its noninvasive nature, deep tissue penetration, and ability to locally activate nanocarriers. This review highlights the recent advances in ultrasound-triggered gas-generating delivery systems, including their design principles, gas-generating mechanisms, and representative nanoplatforms. The mechanistic insights into ultrasound-induced cavitation, thermal effects, and sonodynamic activation are discussed in the context of controlled gas release and drug delivery. Moreover, the therapeutic applications of these systems in solid tumors and metastatic lesions are summarized, and combination strategies integrating ultrasound-triggered gas release with chemotherapy, immunotherapy, or phototherapy are outlined. Finally, the current challenges and future perspectives for clinical translation are addressed, focusing on improving safety, scalability, and patient-specific tailoring. Ultrasound-responsive gas-generating delivery systems represent a promising approach for spatiotemporally controlled cancer therapy.