Investigating the In Vivo Biodistribution of Extracellular Vesicles Isolated from Various Human Cell Sources Using Positron Emission Tomography.

IF 5.4 3区 材料科学 Q2 CHEMISTRY, PHYSICAL
ACS Applied Energy Materials Pub Date : 2024-09-02 Epub Date: 2024-08-20 DOI:10.1021/acs.molpharmaceut.4c00298
Zachary T Rosenkrans, Anna S Thickens, John A Kink, Eduardo Aluicio-Sarduy, Jonathan W Engle, Peiman Hematti, Reinier Hernandez
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Abstract

Positron emission tomography (PET) is a powerful tool for investigating the in vivo behavior of drug delivery systems. We aimed to assess the biodistribution of extracellular vesicles (EVs), nanosized vesicles secreted by cells isolated from various human cell sources using PET. EVs were isolated from mesenchymal stromal cells (MSCs) (MSC EVs), human macrophages (Mϕ EVs), and a melanoma cell line (A375 EVs) by centrifugation and were conjugated with deferoxamine for radiolabeling with Zr-89. PET using conjugated and radiolabeled EVs evaluated their in vivo biodistribution and tissue tropisms. Our study also investigated differences in mouse models, utilizing immunocompetent and immunocompromised mice and an A375 xenograft tumor model. Lastly, we investigated the impact of different labeling techniques on the observed EV biodistribution, including covalent surface modification and membrane incorporation. PET showed that all tested EVs exhibited extended in vivo circulation and generally low uptake in the liver, spleen, and lungs. However, Mϕ EVs showed high liver uptake, potentially attributable to the intrinsic tissue tropism of these EVs from the surface protein composition. MSC EV biodistribution differed between immunocompetent and immunodeficient mice, with increased spleen uptake observed in the latter. PET using A375 xenografts demonstrated efficient tumor uptake of EVs, but no preferential tissue-specific tropism of A375 EVs was found. Biodistribution differences between labeling techniques showed that surface-conjugated EVs had preferential blood circulation and low liver, spleen, and lung uptake compared to membrane integration. This study demonstrates the potential of EVs as effective drug carriers for various diseases, highlights the importance of selecting appropriate cell sources for EV-based drug delivery, and suggests that EV tropism can be harnessed to optimize therapeutic efficacy. Our findings indicate that the cellular source of EVs, labeling technique, and animal model can influence the observed biodistribution.

Abstract Image

利用正电子发射断层扫描研究从不同人类细胞来源分离的细胞外囊泡在体内的生物分布。
正电子发射断层扫描(PET)是研究药物输送系统体内行为的有力工具。我们的目的是利用正电子发射断层扫描评估细胞外小泡(EVs)的生物分布情况,细胞外小泡是由从各种人类细胞来源中分离出来的细胞分泌的纳米级小泡。我们通过离心从间质基质细胞(MSCs)(MSC EVs)、人巨噬细胞(Mϕ EVs)和黑色素瘤细胞系(A375 EVs)中分离出了EVs,并用去氧胺进行了Zr-89的放射性标记。PET 使用共轭和放射性标记的 EVs 评估了它们在体内的生物分布和组织滋养特性。我们的研究还利用免疫功能健全和免疫功能低下的小鼠以及 A375 异种移植肿瘤模型研究了小鼠模型的差异。最后,我们研究了不同标记技术对观察到的 EV 生物分布的影响,包括共价表面修饰和膜结合。PET 显示,所有测试的 EV 在体内循环的时间都较长,在肝、脾和肺中的吸收率普遍较低。然而,Mϕ EVs 在肝脏的摄取率较高,这可能是由于这些 EVs 的表面蛋白成分具有内在的组织趋向性。间叶干细胞EV的生物分布在免疫功能健全小鼠和免疫功能缺陷小鼠之间存在差异,后者的脾脏摄取量增加。使用A375异种移植物进行的PET显示了肿瘤对EVs的有效摄取,但没有发现A375 EVs的组织特异性倾向。不同标记技术的生物分布差异表明,与膜整合相比,表面结合的EVs更倾向于血液循环,而肝脏、脾脏和肺部的摄取量较低。这项研究证明了EVs作为治疗各种疾病的有效药物载体的潜力,强调了为基于EV的药物递送选择适当细胞来源的重要性,并表明可以利用EV的趋向性来优化疗效。我们的研究结果表明,EVs的细胞来源、标记技术和动物模型会影响观察到的生物分布。
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来源期刊
ACS Applied Energy Materials
ACS Applied Energy Materials Materials Science-Materials Chemistry
CiteScore
10.30
自引率
6.20%
发文量
1368
期刊介绍: ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.
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