Yu Kezhi, Huang Yongquan, Wang Yuanyuan, Wu Qunyan, Wang Zihang, Li Fei, Chen Jianri, Yibulayin Maierhaba, Zhang Shushan, Su Zhongzhen, Yan Fei
Department of Ultrasound, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, China.
Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, Shenzhen University Town, Shenzhen, 518055, Guangdong Province, China.
J Nanobiotechnology. 2025 May 14;23(1):344. doi: 10.1186/s12951-025-03377-z.
Ultrasound contrast agents (UCAs) play an important role in diagnosis and the imaging-guided treatment of liver tumor in clinical settings. However, most commercially available UCAs are micro-sized and fabricated through a chemical synthesis route. Here, we developed a new class of biosynthesized nanoscale contrast agent (PEG-GVs) and comprehensively compared its physicochemical characteristics and imaging performance with commercial Sonovue and Sonazoid. Our results revealed PEG-GVs may produce more stable and durable contrast signals, contributing to their penetration beyond blood vessels and long-time retention in liver. Interestingly, we found that PEG-GVs did not exhibit a continuously enhanced accumulation in the liver tumor due to the EPR effect, but displayed a rapid regression. The long-time retention of PEG-GVs in normal liver tissue and rapid regression from liver tumor lead to distinct display of liver tumor boundaries, enabling the early diagnosis of small liver metastases and presenting advantages in guiding radiofrequency ablation of liver tumor. Moreover, we have also verified that PEG-GVs exhibit excellent imaging performance and biosafety in macaques. Our study provides new insights into the roles of PEG-GVs in liver tumor diagnosis and ablation guidance.
超声造影剂（UCAs）在临床肝脏肿瘤的诊断及影像引导治疗中发挥着重要作用。然而，大多数市售的超声造影剂为微米级，通过化学合成路线制备。在此，我们开发了一类新型的生物合成纳米级造影剂（PEG-GVs），并将其理化特性和成像性能与市售的声诺维（Sonovue）和索拉迪德（Sonazoid）进行了全面比较。我们的结果表明，PEG-GVs可能产生更稳定、持久的造影信号，有助于其穿透血管并在肝脏中长期留存。有趣的是，我们发现PEG-GVs并未因增强渗透滞留（EPR）效应而在肝肿瘤中持续增强蓄积，而是呈现快速消退。PEG-GVs在正常肝组织中的长期留存以及从肝肿瘤中的快速消退导致肝肿瘤边界清晰显示，从而能够早期诊断小的肝转移灶，并在引导肝肿瘤射频消融方面具有优势。此外，我们还证实了PEG-GVs在猕猴中表现出优异的成像性能和生物安全性。我们的研究为PEG-GVs在肝肿瘤诊断和消融引导中的作用提供了新的见解。
