Ultrasound activation of liposomes for enhanced ultrasound imaging and synergistic gas and sonodynamic cancer therapy

Ultrasound (US) imaging is widely applied in hospital and clinical settings due to its non-invasiveness, controllability, and high tissue-penetrating ability. Moreover, sonodynamic therapy (SDT) activated by US is a safe cancer therapeutic strategy with a deep tissue penetration effect. Simultaneous integration of US imaging contrast agents, controllable drug delivery vehicles, and effective therapeutic drugs in a single theranostic nanoplatform is a promising strategy for cancer therapy. Herein, we developed a 2,2-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride (AIPH)-loaded liposome (Lip-AIPH) that can simultaneously generate gas bubbles and a high concentration of reactive oxygen species (ROS) under US irradiation. In vivo experimental results confirmed that the generated gas and alkyl radicals were independent of oxygen generation and were successfully used for synergistic gas therapy and SDT in a hypoxic tumor microenvironment. More importantly, the generated gas bubbles, when used as a powerful US contrast agent, greatly enhanced the US contrast to guide cancer therapy. As an US-activated theranostic agent, the liposome enhanced the US imaging and exhibited an improved anticancer efficacy, and it may prove promising for US imaging-guided hypoxic tumor therapy with deep tissue penetration.