M1 Macrophage-Derived Sonoresponsive Nanoparticles for Sonodynamic Anticancer Therapy

BACKGROUND: Many nanocarriers currently developed have potential in tumor targeting, but there are still several limitations to their applications in clinical treatment. It is crucial to explore novel nanocarriers with higher biocompatibility and targeting efficiency to overcome the barriers of the tumor microenvironment to penetrate deeply into the tumor. METHODS: In this work, we designed multilayer sonoresponsive M1/IR780@PLGA nanoparticles, which can actively target tumor tissues, and repolarize M2 macrophages in the tumor microenvironment into M1 macrophages to stimulate antitumor immune effects. When the nanoparticles reach the tumor site, ultrasound (US) irradiation is applied to the tumor site, and the sonosensitizer consumes oxygen and generates ROS, thereby triggering local tumor cell death. RESULTS: The M1/IR780@PLGA nanoparticle-based antitumor sonodynamic therapy (SDT) significantly inhibited tumor growth, triggered a great number of M2 tumor-associated macrophages to convert into M1 macrophages in the tumor microenvironment and promoted dendritic cell maturation to activate the antitumor immune response. CONCLUSION: M1/IR780@PLGA nanoparticles potentiate antitumoral efficacy through SDT and antitumor immune responses by activating dendritic cells maturation and M1 macrophage repolarization in the tumor microenvironment.