超声分子成像利用 B7-H3 靶向微泡增强对肝癌的高强度聚焦超声消融。
Ultrasound Molecular Imaging Enhances High-Intensity Focused Ultrasound Ablation on Liver Cancer With B7-H3-Targeted Microbubbles.
发表日期:2024 Oct
作者:
Xialin Xiong, Hang Zhou, Xinzhi Xu, Qihuan Fu, Yujie Wan, Yuting Cao, Rui Tang, Fang Li, Jun Zhang, Pan Li
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
高强度聚焦超声(HIFU)是一种很有前景的肝癌微创治疗方法;然而,其功效常常受到超声波能量衰减的限制。本研究调查了 B7-H3 靶向微泡 (T-MB) 在增强肝癌 HIFU 消融方面的有效性,并探讨了其临床转化的潜力。T-MB 和同型对照微泡 (I-MB) 通过缀合合成生物素化的抗B7-H3抗体和同种型对照抗体分别作用于微泡表面。通过超声造影来比较不同时间点肝癌中 T-MB 和 I-MB 的积累。通过测量即时肿瘤消融率和长期肿瘤生长抑制来评估 T-MB 增强 HIFU 治疗的功效。此外,通过血清和肿瘤组织中的细胞因子定量以及治疗后第 1、3 和 7 天进行的免疫荧光染色来评估诱导的抗肿瘤免疫反应。T-MB 表现出优异的肝癌特异性积累,其特点是浓度更高与 I-MB 相比,保留时间更长。 T-MB 与 HIFU 的结合显着提高了肿瘤消融率并具有优异的肿瘤生长抑制作用。治疗后分析显示肿瘤微环境中细胞因子水平逐渐上升,抗肿瘤免疫细胞逐渐浸润。T-MBs有效增强HIFU治疗肝癌的疗效,同时促进抗肿瘤免疫反应。这些发现为超声分子成像联合 HIFU 作为肿瘤治疗新方法的临床转化提供了坚实的实验基础。© 2024 作者。约翰·威利出版的癌症医学
High-intensity focused ultrasound (HIFU) is a promising minimally invasive treatment for liver cancer; however, its efficacy is often limited by the attenuation of ultrasonic energy. This study investigates the effectiveness of B7-H3-targeted microbubbles (T-MBs) in enhancing HIFU ablation of liver cancer and explores their potential for clinical translation.T-MBs and isotype control microbubbles (I-MBs) were synthesized through the conjugation of biotinylated anti-B7-H3 antibody and isotype control antibody to the microbubble surface, respectively. Contrast-enhanced ultrasound imaging was performed to compare the accumulation of T-MBs and I-MBs in liver cancer at various time points. The efficacy of T-MBs in enhancing HIFU treatment was evaluated by measuring the immediate tumor ablation rate and long-term tumor growth suppression. Additionally, the induced antitumor immune response was assessed through cytokine quantification in serum and tumor tissue, along with immunofluorescence staining conducted on days 1, 3, and 7 post-treatment.T-MBs demonstrated superior liver cancer-specific accumulation, characterized by higher concentrations and prolonged retention compared to I-MBs. The combination of T-MBs with HIFU resulted in significantly enhanced tumor ablation rates and superior tumor growth suppression. Post-treatment analysis revealed a gradual uptick in cytokine levels within the tumor microenvironment, along with progressive infiltration of antitumor immune cells.T-MBs effectively enhance the therapeutic efficacy of HIFU for liver cancer treatment while simultaneously promoting an antitumor immune response. These findings provide a strong experimental foundation for the clinical translation of ultrasound molecular imaging combined with HIFU as a novel approach for tumor therapy.© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.