An Intelligent Nanotheranostic Agent for Targeting, Redox‐Responsive Ultrasound Imaging, and Imaging‐Guided High‐Intensity Focused Ultrasound Synergistic Therapy

A novel multifunctional nanotheranostic agent with targeting, redox-responsive ultrasound imaging and ultrasound imaging-guided high-intensity focused ultrasound (HIFU) therapy (MSNC-PEG-HA(SS)-PFH, abbreviated as MPH(SS)-PFH) capabilities is developed. The redox-responsive guest molecule release and ultrasound imaging functions can be both integrated in such a "smart" theranostic agent, which is accomplished by the redox-triggered transition from the crosslinking state to retrocrosslinking state of the grafted polyethylene glycol-disulfide hyaluronic acid molecules on the particle surface when reaching a reducing environment in vitro. More importantly, under the tailored ultrasound imaging guiding, in vivo Hela tumor-bearing nude mice can be thoroughly and spatial-accurately ablated during HIFU therapy, due to the targeted accumulation, responsive ultrasound imaging guidance and the synergistic ablation functions of nanotheranostic agent MPH(SS)-PFH in the tumors. This novel multifunctional nano-platform can serve as a promising candidate for further studies on oncology therapy, due to its high stability, responsive and indicative ultrasound imaging of tumors, and enhanced HIFU therapeutic efficiency and spatial accuracy under ultrasound-guidance.