肝肿瘤是最常见恶性肿瘤之一，传统的手术、化疗均存在风险，因此高效、安全的声动力学治疗（SDT）成为极具潜力的治疗手段，但SDT机制尚未清晰。前期基于“连续空化”原理和可逆吸附原理分别制备了新型射频增效剂和CO2纳米炸弹，但两者均不适用于SDT机制研究。本项目以前期工作为基础，以介孔有机硅为载体，表面化学螯合靶向VEGF受体的靶向配体和可逆吸附CO2的改性剂，同时介孔中担载具有化疗特性的声敏剂，并进一步鼓泡吸附CO2，以期构建一种新型SDT增效剂。通过共聚焦、质谱等手段考察低强度聚焦超声（LIFU）以及pH变化对CO2气泡数量、空化剂量以及SDT效果的影响，明确SDT机制。通过考察SDT增效剂在HepG 2肝肿瘤中富集量研究LIFU介导的被动靶向和RGD主动靶向联合靶向机制；进一步利用肿瘤生长曲线、病理学、分子生物学等手段研究SDT与化疗协同治疗肝癌机制，为临床肝癌SDT研究提供新思路。

Liver tumor is one of the most common highly-lethal tumors, and conventional treatment methods, e.g., surgery, chemotherapy, confronted extremely severe risks in treatment safety and side effects. Thus, sonodynamic therapy (SDT) of high efficiency and high safety holds great potentials in liver tumor therapy. However, the disputed principle of SDT remains unresolved, resulting in restriction of SDT towards clinical application. In previous work, basing on principles of ‘continuous cavitaion’ and ‘reversible absorption’, a novel radiofrequency ablation enhancement agents and a smart CO2 ‘nanobomb’ have been successfully obtained, but both are not applicable to principle investigation of SDT. In this project, Basing on the theoretical basis of previous work, a type of novel SDT enhancement agents that encapsulates sonosensitizers of chemotherapy property and chemically adsorbs CO2 via bubbling route will be constructed, wherein mesoporous organicsilica nanoparticles (MON) are employed as the main building blocks, and their surfaces are chemically chelated by RGD ligands capable of modified agents capable of reversibly adsorbing CO2 and targeting vascular endothelial growth factor (VEGF) receptor in sequence. Influences from variation of the parameters of low-intensity focused ultrasound (LIFU) and pH on the number of CO2 bubbles, cavitation dose and SDT outcomes can be explored via a series of methods, e.g., confocal, mass spectrometer, steady state and transient state fluorescence spectrometer, electron spin resonance, etc., ultimately validating the principle of SDT. The mechanism of marriage targeting consisting of LIFU-mediated passive targeting and RGD-mediated active targeting will be explored, and afterwards basing this, the principle of synergistic treatment of SDT and chemotherapy will be evaluated and investigated via profile monitoring of tumor growth, pathological examination, molecular characterization, paving a new route to SDT for liver tumor.