Chemical Modulation of Bioengineered Exosomes for Tissue-Specific Biodistribution
Chemical Modulation of Bioengineered Exosomes for Tissue-Specific Biodistribution
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DOI：
10.1002/adtp.201900111
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发表时间：
2019-11-01
影响因子：
4.6
通讯作者：
Choi, Hak Soo
中科院分区：
文献类型：
--
作者：
Hwang, Do Won;Jo, Min Joo;Choi, Hak Soo
纳米材料的物理化学性质通过减少非特异性背景摄取以及控制生物分布和清除在组织特异性靶向中发挥关键作用。由于表面化学的强烈影响，用可充电和可追踪的小分子荧光团对生物惰性外体进行化学调节对最终偶联物的靶向性、稳定性和毒性有重大影响。在本研究中，电荷可变外泌体是通过将其表面蛋白与近红外荧光基团结合来设计的，以控制外泌体的体内命运。有趣的是，两性离子荧光团标记的外泌体显示出快速的肾脏清除，很少甚至没有非特异性组织摄取，而阴离子外泌体通过肝胆途径排泄，在肝脏中具有高摄取。外泌体偶联物的生物分布和药代动力学与它们相应的自由荧光团相当，表明表面特性决定了最终偶联物在生物体中的命运。这种化学调节外泌体的独特表面特性在皮内给药后的淋巴系统中得到证实，这导致了次级淋巴组织中独特的动力学特征。这一发现可以作为开发组织特异性外泌体疗法的基础。
The physicochemical properties of nanomaterials play a key role in tissue-specific targeting by reducing nonspecific background uptake as well as controlling biodistribution and clearance. Due to the strong influence of surface chemistry, chemical modulation of bioinert exosomes with chargeable and traceable small molecule fluorophores has a significant effect on the targeting, stability, and toxicity of the final conjugates. In this study, charge-variable exosomes are designed by conjugating their surface proteins with near-infrared fluorophores to control the in vivo fate of exosomes. Interestingly, zwitterionic fluorophore-labeled exosomes show rapid renal clearance with minimum to none nonspecific tissue uptake, whereas anionic exosomes are excreted through the hepatobiliary route with high uptake in the liver. The biodistribution and pharmacokinetics of exosome conjugates are comparable to their corresponding free fluorophores, demonstrating that the surface characteristics govern the fate of final conjugates in the living organism. Such unique surface properties of chemically modulated exosomes are confirmed in the lymphatic system after intradermal administration, which results in distinctive kinetic profiles in the secondary lymphoid tissues. This finding can subsequently serve as the foundation for developing tissue-specific exosome-based therapeutics.