Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy.
Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy.
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DOI：
10.1002/adma.201706616
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Stevens MM
中科院分区：
文献类型：
--
作者：
Fuhrmann G;Chandrawati R;Parmar PA;Keane TJ;Maynard SA;Bertazzo S;Stevens MM
细胞外小泡作为细胞间通讯的重要媒介、潜在的药物载体和疾病的生物标志物，近年来受到了广泛的关注。这些天然细胞衍生的纳米颗粒被认为是生物相容的，在生理条件下稳定，与其他合成纳米颗粒相比，表现出较低的免疫原性。尽管最初的临床试验仍在进行中，但EVS在治疗应用中的使用可能会受到限制，因为不受欢迎的非靶向活性和全身给药可能会影响它们到达目标组织的能力的“稀释效应”。为了充分开发其治疗潜力，电动汽车被嵌入到可植入的生物材料中，旨在利用酶前药物疗法(EPT)实现局部治疗。在EVS用于EPT方法的首次应用中，EVS被用作智能载体，用于稳定水凝胶中的酶，以实现良性前体药物到活性抗炎化合物的局部受控转化。结果表明，天然EVS的抗炎能力与合成载体相当或更好，特别是在反复长期孵育和不同的巨噬细胞炎症模型中。此外，本文还介绍了水凝胶中EVS的密度相关彩色扫描电子显微镜成像，这是进一步了解生物环境中EVS的有效工具。
Extracellular vesicles (EVs) have recently gained significant attention as important mediators of intercellular communication, potential drug carriers, and disease biomarkers. These natural cell-derived nanoparticles are postulated to be biocompatible, stable under physiological conditions, and to show reduced immunogenicity as compared to other synthetic nanoparticles. Although initial clinical trials are ongoing, the use of EVs for therapeutic applications may be limited due to undesired off-target activity and potential “dilution effects” upon systemic administration which may affect their ability to reach their target tissues. To fully exploit their therapeutic potential, EVs are embedded into implantable biomaterials designed to achieve local delivery of therapeutics taking advantage of enzyme prodrug therapy (EPT). In this first application of EVs for an EPT approach, EVs are used as smart carriers for stabilizing enzymes in a hydrogel for local controlled conversion of benign prodrugs to active antiinflammatory compounds. It is shown that the natural EVs’ antiinflammatory potential is comparable or superior to synthetic carriers, in particular upon repeated long-term incubations and in different macrophage models of inflammation. Moreover, density-dependent color scanning electron microscopy imaging of EVs in a hydrogel is presented herein, an impactful tool for further understanding EVs in biological settings.
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