Oxygen‐sufficient lipid nanobubbles combined with UTMD for enhanced sonodynamic therapy of Hep‐G2 cells

Abstract Sonodynamic therapy (SDT) is an emerging noninvasive therapeutic approach, which could penetrate deep‐seated tissues and activate sonosensitizer to produce cytotoxic reactive oxygen species (ROS). Nevertheless, the hypoxic tumor microenvironment significantly limits the efficiency of SDT due to its oxygen‐consumption treatment principle. To break hypoxia‐induced resistance and improve the efficacy of SDT, we developed shell‐core structured oxygen‐sufficient nanobubbles(NBs), which were designed with a lipid shell loaded the sonosensitizer IR780 and a gas core loaded with oxygen. With the aid of ultrasound‐targeted microbubble destruction (UTMD), IR780@O 2 NBs not only make sonosensitizers more effectively enriched at the tumor site in a controlled manner, but also directly mediate oxygen release and provide sufficient oxygen for producing more ROS to induce cell apoptosis. Thus, IR780@O 2 NBs can efficiently inhibit the proliferation of Hep‐G2 cells under ultrasound exposure. What is more, IR780@O 2 NBs have a potential for contrast enhanced ultrasound (CEUS) imaging. We believe that our oxygen‐sufficient NBs trigged by UTMD could be an ideal therapeutic and imaging system for hepatocellular carcinoma.