State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, People's Republic of China.
Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Int J Nanomedicine. 2020 Mar 17;15:1871-1888. doi: 10.2147/IJN.S238398. eCollection 2020.
The high-intensity focused ultrasound (HIFU) ablation of tumors is inseparable from synergistic agents and image monitoring, but the existing synergistic agents have the defects of poor targeting and a single imaging mode, which limits the therapeutic effects of HIFU. The construction of a multifunctional biological targeting synergistic agent with high biosafety, multimodal imaging and targeting therapeutic performance has great significance for combating cancer.
Multifunctional biological targeting synergistic agent consisting of (), ICG and PFH coloaded cationic lipid nanoparticles (CL-ICG-PFH-NPs) were constructed for targeting multimode imaging, synergistic effects with HIFU and imaging-guided ablation of tumors, which was evaluated both in vitro and in vivo.
Both in vitro and in vivo systematical studies validated that the biological targeting synergistic agent can simultaneously achieve tumor-biotargeted multimodal imaging, HIFU synergism and multimodal image monitoring in HIFU therapy. Importantly, the electrostatic adsorption method and the targeting of to tumor tissues allow the CL-ICG-PFH-NPs to be retained in the tumor tissue, achieve the targeting ability of synergistic agent. Multimodal imaging chose the best treatment time according to the distribution of nanoparticles in the body to guide the efficient and effective treatment of HIFU. CL-ICG-PFH-NPs could serve as a phase change agent and form microbubbles that can facilitate HIFU ablation by mechanical effects, acoustic streaming and shear stress. This lays a foundation for the imaging and treatment of tumors.
In this work, a biological targeting synergistic agent was successfully constructed with good stability and physicochemical properties. This biological targeting synergistic agent can not only provide information for early diagnosis of tumors but also realize multimodal imaging monitoring during HIFU ablation simultaneously with HIFU treatment, which improves the shortcomings of HIFU treatment and has broad application prospects.
高强度聚焦超声（HIFU）消融肿瘤离不开协同剂和图像监测，但现有的协同剂存在靶向性差、成像模式单一等缺陷，限制了 HIFU 的治疗效果。构建一种具有高生物安全性、多模式成像和靶向治疗性能的多功能生物靶向协同剂，对于癌症的治疗具有重要意义。
构建了由（）、ICG 和 PFH 共载阳离子脂质纳米粒（CL-ICG-PFH-NPs）组成的多功能生物靶向协同剂，用于靶向多模式成像、与 HIFU 的协同作用以及肿瘤的成像引导消融，在体外和体内进行了评价。
体外和体内系统研究均验证了该生物靶向协同剂可同时实现肿瘤靶向多模式成像、HIFU 协同作用以及 HIFU 治疗中的多模式图像监测。重要的是，通过静电吸附方法和对肿瘤组织的靶向作用，使 CL-ICG-PFH-NPs 能够保留在肿瘤组织中，实现协同剂的靶向能力。多模式成像根据纳米粒在体内的分布选择最佳的治疗时间，以指导 HIFU 的高效、有效治疗。CL-ICG-PFH-NPs 可以作为相变剂并形成微泡，通过机械效应、声流和剪切力促进 HIFU 消融。这为肿瘤的成像和治疗奠定了基础。
本研究成功构建了一种具有良好稳定性和理化性质的生物靶向协同剂。该生物靶向协同剂不仅可以为肿瘤的早期诊断提供信息，还可以在 HIFU 消融的同时实现多模式成像监测，同时改善了 HIFU 治疗的不足，具有广阔的应用前景。
