超声响应的GPC3靶向及超声敏感剂的可视化肝细胞癌治疗纳米递送系统

Ultrasound-Responsive Nanodelivery System of GPC3-Targeting and Sonosensitizer for Visualized Hepatocellular Carcinoma Therapy

International Journal of Nanomedicine

影响因子:6.5

分区:医学2区 / 药学2区纳米科技3区

发表日期:2024

作者: Juying Zhang, Xia Luo, Xin Yang, Hanmei Li, Qiong Jiang, You Yang, Menglin Luo, Zijun Ma, Ping He, Linli Feng, Ling Li, Maochun Zhang, Yang Li, Jinhong Yu

DOI: 10.2147/IJN.S470847

摘要

肝细胞癌（Hepatocellular carcinoma, HCC）的发病率持续上升，死亡率仍然很高，因此需要更有效的策略改善HCC的治疗。本研究中，我们报告了一种可视化的GPC3靶向纳米递送系统（命名为GC-NBs）结合超声声动力学治疗（SDT），以增强HCC的治疗效果。该纳米递送系统能够主动靶向肝细胞癌细胞，并在低强度超声照射下通过相变形成纳米气泡，实现超声成像。同时，纳米气泡崩溃后释放的氯酮酮（Ce6）在超声照射下产生活性氧（ROS），诱导SDT。体内外实验均显示，GC-NBs能够在肿瘤区域积累，并在GPC3抗体（GPC3-Ab）引导下实现超声引导的抗肿瘤治疗。该纳米系统未显示明显的生物毒性，并且可以通过超声成像实现个性化治疗监测。GC-NBs结合肿瘤特异性靶向和刺激响应性控释，提供了一种可视化的抗肿瘤策略，从靶向声动力学角度实现精准治疗。

Abstract

The incidence of hepatocellular carcinoma (HCC) is continuously increasing, and the mortality rate remains high. Thus, more effective strategies are needed to improve the treatment of HCC.In this study, we report the use of a visualized glypican-3 (GPC3)-targeting nanodelivery system (named GC-NBs) in combination with sonodynamic therapy (SDT) to enhance the therapeutic efficacy for treating HCC. The obtained nanodelivery system could actively target hepatocellular carcinoma cells and achieve ultrasound imaging through phase changes into nanobubbles under low-intensity ultrasound irradiation. Meanwhile, the released chlorine e6 (Ce6) after the nanobubbles collapse could lead to the generation of reactive oxygen species (ROS) under ultrasound irradiation to induce SDT.Both in vitro and in vivo experiments have shown that GC-NBs can accumulate in tumour areas and achieve sonodynamic antitumour therapy under the navigation action of glypican-3-antibody (GPC3-Ab). Furthermore, in vitro and in vivo experiments did not show significant biological toxicity of the nanodelivery system. Moreover, GC-NBs can be imaged with ultrasound, providing personalized treatment monitoring.GC-NBs enable a visualized antitumour strategy from a targeted sonodynamic perspective by combining tumour-specific targeting and stimuli-responsive controlled release into a single system.