Cavitation‐Inducible Mesoporous Silica–Titania Nanoparticles for Cancer Sonotheranostics

Sonodynamic therapy has received increasing attention for cancer treatments as an alternative to photodynamic therapy. However, its clinical applications have been limited by the lack of a sonosensitizer that is capable of producing sufficient amounts of reactive oxygen species (ROS) in response to ultrasound (US) exposure. Herein, PEGylated mesoporous silica–titania nanoparticles (P‐MSTNs) are prepared and used as US‐responsive nanocarriers for cancer sonotheranostics. Perfluorohexane (PFH), which is chosen as the gas precursor, is physically encapsulated into P‐MSTNs using the oil‐in‐water emulsion method. Owing to the vaporization of the gas precursor, PFH@P‐MSTNs (137 nm in diameter) exhibit a strong photoacoustic signal in vivo for at least 6 h. Compared to P‐MSTNs, PFH@P‐MSTNs generate significantly higher amounts of ROS due to the nanobubble‐induced cavitation in the presence of US. When systemically administered to tumor‐bearing mice, PFH@P‐MSTNs effectively accumulate in the tumor site due to the passive targeting mechanism. Consequently, PFH@P‐MSTNs show much higher antitumor efficacy than P‐MSTNs due to the enhanced cavitation‐mediated ROS generation in response to US exposure. It is considered that PFH@P‐MSTNs may hold significant potential for cancer sonotheranostics. A perfluorocarbon‐loaded nanosensitizer is developed for cancer sonotheranostics. The gas precursor in a nanosensitizer enables long‐term photoacoustic imaging as well as enhanced cavitation due to its vaporization. The nanosensitizers effectively accumulate in the tumor tissue after their systemic administration to tumor‐bearing mice. Consequently, the perfluorocarbon‐loaded nanosensitizers show significant potential as sonotheranostic agents for photoacoustic imaging and sonodynamic therapy of cancer.