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, Fe₃O₄ NPs), denote as Fe₃O₄-LA-PLGA NPs. The Fe₃O₄-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 Fe₃O₄ NPs were rapidly released from the PLGA NPs. It was demonstrated that LA could spontaneously react with hydrogen peroxide (H₂O₂) present in the tumor microenvironment to generate NO for gas therapy. Concurrently, Fe₃O₄ NPs could rapidly react with H₂O₂ 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.