Chongqing Key Laboratory of Ultrasound Molecular Imaging & Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Department of Ultrasound, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Int J Nanomedicine. 2022 Jan 25;17:333-350. doi: 10.2147/IJN.S336632. eCollection 2022.
Therapeutic ultrasound (US) has been extensively explored for its inherent high tissue-penetrating capability and on-demand irradiation without radioactive damage. Although high-intensity focused ultrasound (HIFU) is evolved as such an outstanding US-based approach, its insufficient therapeutic effect and the high-intensity induced potential damage to surrounding normal tissues hindered its development towards practical application. As opposed to high intensity ultrasound, sonodynamic therapy (SDT) is a low intensity US-based method which exhibits certain therapeutic effects against cancer via sonosensitizers-generated reactive oxygen species (ROS) overproduction.
Hematoporphyrin monomethyl ether (HMME) loaded CaCO nanoparticles (designated as Ca@H) were synthesized by a gas diffusion method. The pH-responsive performance, in vitro SDT, ex vivo HIFU therapy (HIFUT), photoacoustic (PA) imaging and in vivo HIFUT combined with SDT were investigated thoroughly.
Ca@H NPs gradually decomposed in acid tumor microenvironment, produced CO and released HMME. Both CO and HMME enhanced photoacoustic (PA) imaging. The generated CO bubbles also enhanced HIFUT by inducing an enlarged ablation area. The tumor ablation efficiency (61.04%) was significantly improved with a combination of HIFU therapy and SDT.
pH-responsive Ca@H NPs have been successfully constructed for PA imaging-guided/monitored HIFUT combined with SDT. With the assistance of pH-responsive Ca@H NPs, the combination of these two US-based therapies is expected to play a role in the treatment of non-invasive tumor in the future.
治疗超声（US）因其具有固有高组织穿透能力和按需照射而无放射性损伤的特点，已被广泛探索。虽然高强度聚焦超声（HIFU）已发展成为一种出色的基于 US 的方法，但由于其治疗效果不足以及高强度对周围正常组织的潜在损伤，限制了其向实际应用的发展。与高强度超声相反，声动力学疗法（SDT）是一种基于低强度超声的方法，通过声敏剂产生的过量活性氧物质（ROS）来发挥对癌症的一定治疗作用。
通过气体扩散法合成了血卟啉单甲醚（HMME）负载的 CaCO 纳米颗粒（命名为 Ca@H）。深入研究了其 pH 响应性能、体外 SDT、离体 HIFU 治疗（HIFUT）、光声（PA）成像以及体内 HIFUT 联合 SDT。
Ca@H NPs 在酸性肿瘤微环境中逐渐分解，产生 CO 和释放 HMME。CO 和 HMME 均增强了光声（PA）成像。生成的 CO 气泡还通过诱导扩大的消融区域来增强 HIFUT。HIFU 治疗联合 SDT 可显著提高肿瘤消融效率（61.04%）。
成功构建了 pH 响应性 Ca@H NPs 用于 PA 成像引导/监测的 HIFUT 联合 SDT。在 pH 响应性 Ca@H NPs 的辅助下，这两种基于 US 的治疗方法的联合有望在未来发挥作用，用于治疗非侵入性肿瘤。
