State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences , Shanghai 200050, People's Republic of China.
University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
ACS Nano. 2017 Sep 26;11(9):9093-9102. doi: 10.1021/acsnano.7b03772. Epub 2017 Aug 16.
High intensity focused ultrasound (HIFU) surgery generally suffers from poor precision and low efficiency in clinical application, especially for cancer therapy. Herein, a multiscale hybrid catalytic nanoreactor (catalase@MONs, abbreviated as C@M) has been developed as a tumor-sensitive contrast and synergistic agent (C&SA) for ultrasound-guided HIFU cancer surgery, by integrating dendritic-structured mesoporous organosilica nanoparticles (MONs) and catalase immobilized in the large open pore channels of MONs. Such a hybrid nanoreactor exhibited sensitive catalytic activity toward HO, facilitating the continuous O gas generation in a relatively mild manner even if incubated with 10 μM HO, which finally led to enhanced ablation in the tissue-mimicking PAA gel model after HIFU exposure mainly resulting from intensified cavitation effect. The C@M nanoparticles could be accumulated within the HO-enriched tumor region through enhanced permeability and retention effect, enabling durable contrast enhancement of ultrasound imaging, and highly efficient tumor ablation under relatively low power of HIFU exposure in vivo. Very different from the traditional perfluorocarbon-based C&SA, such an on-demand catalytic nanoreactor could realize the accurate positioning of tumor without HIFU prestimulation and efficient HIFU ablation with a much safer power output, which is highly desired in clinical HIFU application.
高强度聚焦超声（HIFU）手术在临床应用中通常存在精度差和效率低的问题，尤其是在癌症治疗方面。在此，我们开发了一种多尺度杂化催化纳米反应器（catalase@MONs，简称 C@M），作为一种肿瘤敏感的对比剂和协同剂（C&SA），用于超声引导的 HIFU 癌症手术，该纳米反应器通过整合树枝状结构的介孔有机硅纳米粒子（MONs）和固定在 MONs 大孔道中的过氧化氢酶。这种杂化纳米反应器对 HO 具有敏感的催化活性，即使在孵育 10 μM HO 的情况下，也能以相对温和的方式持续产生 O 气体，这最终导致在 HIFU 暴露后的组织模拟 PAA 凝胶模型中增强消融，主要是由于空化效应的增强。C@M 纳米粒子可以通过增强的通透性和保留效应在富含 HO 的肿瘤区域积累，从而实现超声成像的持久对比增强，并在体内相对较低的 HIFU 辐射功率下实现高效的肿瘤消融。与传统的全氟碳基 C&SA 非常不同，这种按需催化纳米反应器可以在没有 HIFU 预刺激的情况下实现肿瘤的精确定位，并以更安全的功率输出实现高效的 HIFU 消融，这在临床 HIFU 应用中是非常需要的。
