Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, People's Republic of China.
University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
Int J Nanomedicine. 2021 Dec 29;16:8405-8416. doi: 10.2147/IJN.S342614. eCollection 2021.
Ultrasonic molecular imaging (UMI) technology has attracted increasing interest because of its low cost and capability to evaluate changes rapidly and noninvasively at the cellular and molecular levels. The key material of this technology is ultrasound-responsive gas vesicles (GVs). GVs synthesized by conventional chemical methods have several limitations, such as high costs, low yields, and complex production processes. In comparison, biosynthesized GVs have the advantages of high stability, a low risk of toxicity, genetic engineering characterization, easy post modification and drug loading potential. However, translational studies of their biosynthesis are still in their infancy; in particular, the duration of GVs in the circulatory system is essential for the usage of UMI in biomedicine and the clinic.
Here, we report novel GVs biosynthesized by the cyanobacterium , which have a moderate size, a negative zeta potential, a rod-like morphology, and a protein-shelled gas-contained structure. These GVs without any chemical modifications could be detected in the mice circulatory system for more than 10 hours by clinically used ultrasound scanners. In particular, GVs can accumulate in tumors via the enhanced permeation and retention (EPR) effect 11 hours post-injection, and lasting at least 2 hours, which might be a potential aid for tumor diagnosis. Furthermore, pathological and hematological study suggested that GVs are safe for the host.
We concluded that the GVs synthesized by without any modifications have UMI potential for systemic evaluation as well as tumoral diagnosis after intravenous injection.
超声分子成像是一种新型的分子影像学技术,具有成本低、能够在细胞和分子水平上快速进行非侵入性评估等优点,因此受到了越来越多的关注。该技术的关键材料是超声响应性气穴(GVs)。通过传统化学方法合成的 GVs 存在成本高、产率低、生产工艺复杂等局限性。相比之下,生物合成的 GVs 具有稳定性高、毒性风险低、遗传工程表征、易于后期修饰和药物负载潜力等优点。然而,其生物合成的转化研究仍处于起步阶段;特别是 GVs 在循环系统中的半衰期对于 UMI 在生物医学和临床中的应用至关重要。
在这里,我们报告了一种新型的 GVs,由蓝藻生物合成,具有中等大小、负 ζ 电位、棒状形态和蛋白壳气体包含结构。这些未经任何化学修饰的 GVs 可以在临床使用的超声扫描仪中在小鼠循环系统中检测到超过 10 小时。特别是,GVs 可以通过增强渗透和保留(EPR)效应在注射后 11 小时内聚集在肿瘤中,并持续至少 2 小时,这可能是肿瘤诊断的潜在辅助手段。此外,病理和血液学研究表明 GVs 对宿主是安全的。
我们得出结论,未经任何修饰的 合成的 GVs 具有 UMI 潜力,可用于静脉注射后的全身评估和肿瘤诊断。