Ultrasound-responsive nanoparticles for nitric oxide release to inhibit the growth of breast cancer.

Gas therapy represents a promising strategy for cancer treatment, with nitric oxide (NO) therapy showing particular potential in tumor therapy. However, ensuring sufficient production of NO remains a significant challenge. Leveraging ultrasound-responsive nanoparticles to promote the release of NO is an emerging way to solve this challenge. In this study, we successfully constructed ultrasound-responsive nanoparticles, which consisted of poly (D, L-lactide-co-glycolic acid) (PLGA) nanoparticles, natural L-arginine (LA), and superparamagnetic iron oxide nanoparticles (SPIO, FeO NPs), denote as FeO-LA-PLGA NPs. The FeO-LA-PLGA NPs exhibited effective therapeutic effects both in vitro and in vivo, particularly in NO-assisted antitumor gas therapy and photoacoustic (PA) imaging properties. Upon exposure to ultrasound irradiation, LA and FeO NPs were rapidly released from the PLGA NPs. It was demonstrated that LA could spontaneously react with hydrogen peroxide (HO) present in the tumor microenvironment to generate NO for gas therapy. Concurrently, FeO NPs could rapidly react with HO to produce a substantial quantity of reactive oxygen species (ROS), which can oxidize LA to further facilitate the release of NO. In conclusion, the proposed ultrasound-responsive NO delivery platform exhibits significant potential in effectively inhibiting the growth of breast cancer.