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Hedgehog-inspired immunomagnetic beads for high-efficient capture and release of exosomes
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2022-04-22 , DOI: 10.1039/d2tb00226d Jia Cheng 1 , Nanhang Zhu 1 , Yujia Zhang 1 , Yue Yu 1 , Ke Kang 1 , Qiangying Yi 1 , Yao Wu 1
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2022-04-22 , DOI: 10.1039/d2tb00226d Jia Cheng 1 , Nanhang Zhu 1 , Yujia Zhang 1 , Yue Yu 1 , Ke Kang 1 , Qiangying Yi 1 , Yao Wu 1
Affiliation
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Exosomes are small extracellular vesicles secreted by cells. They play an important regulatory role in the physiological and pathological processes of the body, and participate in the occurrence and development of many diseases. Although tumor-derived exosomes have been used as biomarkers for cancer detection, it is still a huge challenge to efficiently capture and release functionally complete exosomes. In our research, inspired by the structure of hedgehog burrs, we proposed immunomagnetic hedgehog particles (IMHPs) to efficiently capture and release exosomes. In general, after the assembly of one-dimensional nanostructural TiO2 bundles into hedgehog TiO2 particles with 356.12 ± 38.32 nm spikes, magnetic responsive nanoparticles (Fe3O4, ∼20 nm), an antifouling polyethylene glycol (PEG) component containing a redox responsive disulfide linkage and anti-CD63 antibody were introduced stepwise to functionalize hedgehog particles and generate IMHPs (1.23 ± 0.18 μm). Due to their unique topological structures, exosomes were positively selected with an exosomal marker (CD63) and negatively selected by depleting environmental pollutants (protein precipitates, cell debris) with the nano-spikes. These prepared IMHPs were successfully applied to capture exosomes from MCF-7 cells, with a capture efficiency of 91.70%. Then, tris (2-carboxyethyl) phosphine hydrochloride (TCEP) was used to reduce the disulfide bond to release exosomes, and the release efficiency was up to 82.45%. The exosomes that experienced successive immunomagnetic separation and release well maintained their structural integrity and good bioactivity to promote MCF-7 cell migration, as compared with those exosomes separated by the classic ultracentrifugation approach. These results also indicated that IMHPs would have broad prospects in biomedicine and clinical applications, where highly efficient and non-destructive separation of bio-substances (cells, extracellular vesicles, etc.) is critically required.
中文翻译：
用于高效捕获和释放外泌体的受 Hedgehog 启发的免疫磁珠
外泌体是细胞分泌的小细胞外囊泡。它们在机体的生理和病理过程中起着重要的调节作用，并参与了许多疾病的发生和发展。尽管肿瘤衍生的外泌体已被用作癌症检测的生物标志物，但有效捕获和释放功能完整的外泌体仍然是一个巨大的挑战。在我们的研究中，受刺猬毛刺结构的启发，我们提出了免疫磁性刺猬颗粒 (IMHPs) 来有效捕获和释放外泌体。一般来说，一维纳米结构TiO 2束组装成具有356.12±38.32 nm尖峰的刺猬型TiO 2颗粒后，磁响应纳米颗粒（Fe 3 O 4，~20 nm），逐步引入含有氧化还原响应性二硫键和抗CD63抗体的防污聚乙二醇（PEG）组分以使hedgehog颗粒功能化并产生IMHP（1.23±0.18μm）。由于其独特的拓扑结构，外泌体通过外泌体标记（CD63）进行正选择，并通过纳米尖峰消耗环境污染物（蛋白质沉淀物、细胞碎片）进行负选择。这些制备的 IMHP 成功应用于从 MCF-7 细胞中捕获外泌体，捕获效率为 91.70%。然后用三(2-羧乙基)膦盐酸盐(TCEP)还原二硫键释放外泌体，释放效率高达82.45%。与经典超速离心分离的外泌体相比，经过连续免疫磁分离和释放的外泌体保持了结构完整性和良好的生物活性，以促进 MCF-7 细胞迁移。这些结果还表明，IMHPs在生物医学和临床应用中具有广阔的前景，可以高效、无损地分离生物物质（细胞、细胞外囊泡、等）是至关重要的。
更新日期：2022-04-22
中文翻译：
用于高效捕获和释放外泌体的受 Hedgehog 启发的免疫磁珠
外泌体是细胞分泌的小细胞外囊泡。它们在机体的生理和病理过程中起着重要的调节作用，并参与了许多疾病的发生和发展。尽管肿瘤衍生的外泌体已被用作癌症检测的生物标志物，但有效捕获和释放功能完整的外泌体仍然是一个巨大的挑战。在我们的研究中，受刺猬毛刺结构的启发，我们提出了免疫磁性刺猬颗粒 (IMHPs) 来有效捕获和释放外泌体。一般来说，一维纳米结构TiO 2束组装成具有356.12±38.32 nm尖峰的刺猬型TiO 2颗粒后，磁响应纳米颗粒（Fe 3 O 4，~20 nm），逐步引入含有氧化还原响应性二硫键和抗CD63抗体的防污聚乙二醇（PEG）组分以使hedgehog颗粒功能化并产生IMHP（1.23±0.18μm）。由于其独特的拓扑结构，外泌体通过外泌体标记（CD63）进行正选择，并通过纳米尖峰消耗环境污染物（蛋白质沉淀物、细胞碎片）进行负选择。这些制备的 IMHP 成功应用于从 MCF-7 细胞中捕获外泌体，捕获效率为 91.70%。然后用三(2-羧乙基)膦盐酸盐(TCEP)还原二硫键释放外泌体，释放效率高达82.45%。与经典超速离心分离的外泌体相比，经过连续免疫磁分离和释放的外泌体保持了结构完整性和良好的生物活性，以促进 MCF-7 细胞迁移。这些结果还表明，IMHPs在生物医学和临床应用中具有广阔的前景，可以高效、无损地分离生物物质（细胞、细胞外囊泡、等）是至关重要的。
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