Echogenic Exosomes as ultrasound contrast agents.
Echogenic Exosomes as ultrasound contrast agents.
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DOI：
10.1039/d0na00339e
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发表时间：
2020-08-01
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
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外泌体是自然分泌的细胞外双层囊泡（直径40-130 nm），最近被发现在细胞间通讯和生物分子传递中起关键作用。它们独特的特性——稳定性、渗透性、生物相容性和低免疫原性——使它们成为输送癌症治疗药物和其他天然产物的首选候选材料。在这里，我们提出了回声外泌体的第一份报告，它结合了传统微泡的声学响应性与外泌体的非免疫原性和小尺寸形态的优点。微泡虽然是有效的超声造影剂，但由于其体积大，限制了血管内使用。在目前的研究中，我们通过在甘露醇的存在下冷冻干燥，使牛奶衍生的外泌体具有回声性。利用超声成像和直接测量线性和非线性散射响应来研究制备的外泌体的回声性和稳定性。商用扫描仪显示，在5 mg mL−1时存在回声外泌体，超声图像亮度增强（40 MHz时28.9%）。在40 μg mL−1浓度下，外泌体表现出显著的线性和非线性散射响应，基频增强11 dB，次谐波增强8.5 dB，次谐波增强3.5 dB。将回声外泌体注射到小鼠的尾静脉和大鼠的滑液中，可显著提高超声图像的亮度——高达300%，显示出它们在各种体内应用中的前景。回声外泌体具有可大规模从牛乳中提取，无毒性和最小的免疫原性反应，在本研究中成功地用作超声造影剂，并提供了一个令人兴奋的可能性，作为一种有效的超声反应性药物递送系统。外泌体是自然分泌的细胞外双层囊泡（直径40-130 nm），具有回声（对超声有反应），这使得它们有可能作为药物输送和超声成像的双重介质。
Exosomes are naturally secreted extracellular bilayer vesicles (diameter 40–130 nm), which have recently been found to play a critical role in cell-to-cell communication and biomolecule delivery. Their unique characteristics—stability, permeability, biocompatibility and low immunogenicity—have made them a prime candidate for use in delivering cancer therapeutics and other natural products. Here we present the first ever report of echogenic exosomes, which combine the benefits of the acoustic responsiveness of traditional microbubbles with the non-immunogenic and small-size morphology of exosomes. Microbubbles, although effective as ultrasound contrast agents, are restricted to intravascular usage due to their large size. In the current study, we have rendered bovine milk-derived exosomes echogenic by freeze drying them in the presence of mannitol. Ultrasound imaging and direct measurement of linear and nonlinear scattered responses were used to investigate the echogenicity and stability of the prepared exosomes. A commercial scanner registered enhancement (28.9% at 40 MHz) in the brightness of ultrasound images in presence of echogenic exosomes at 5 mg mL−1. The exosomes also showed significant linear and nonlinear scattered responses—11 dB enhancement in fundamental, 8.5 dB in subharmonic and 3.5 dB in second harmonic all at 40 μg mL−1 concentration. Echogenic exosomes injected into the tail vein of mice and the synovial fluid of rats resulted in significantly higher brightness—as much as 300%—of the ultrasound images, showing their promise in a variety of in vivo applications. The echogenic exosomes, with their large-scale extractability from bovine milk, lack of toxicity and minimal immunogenic response, successfully served as ultrasound contrast agents in this study and offer an exciting possibility to act as an effective ultrasound responsive drug delivery system. Exosomes, naturally secreted extracellular bilayer vesicles (diameter 40–130 nm), have been rendered echogenic (responsive to ultrasound) allowing their potential use as a dual agent for drug delivery and ultrasound imaging.
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