A novel surface functionalization platform to prime extracellular vesicles for targeted therapy and diagnostic imaging

IF 4.7 4区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Nanomedicine: Nanotechnology, Biology and Medicine Pub Date : 2023-01-01 DOI:10.1016/j.nano.2022.102607

Besmira Sabani MSc , Michael Brand PhD , Ina Albert Dr. scient. med. , Joelle Inderbitzin MSc , Fritz Eichenseher PhD , Mathias Schmelcher PhD , Jack Rohrer PhD , Rainer Riedl PhD , Steffi Lehmann PhD

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引用次数: 3

Abstract

Extracellular vesicles (EVs), nanovesicles released by cells to effectively exchange biological information, are gaining interest as drug delivery system. Yet, analogously to liposomes, they show short blood circulation times and accumulation in the liver and the spleen. For tissue specific delivery, EV surfaces will thus have to be functionalized. We present a novel platform for flexible modification of EVs with target-specific ligands based on the avidin-biotin system. Genetic engineering of donor cells with a glycosylphosphatidylinositol-anchored avidin (GPI-Av) construct allows the isolation of EVs displaying avidin on their surface, functionalized with any biotinylated ligand. For proof of concept, GPI-Av EVs were modified with i) a biotinylated antibody or ii) de novo designed and synthesized biotinylated ligands binding carbonic anhydrase IX (CAIX), a membrane associated enzyme overexpressed in cancer. Functionalized EVs showed specific binding and uptake by CAIX-expressing cells, demonstrating the power of the system to prepare EVs for cell-specific drug delivery.

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一种新的表面功能化平台，为靶向治疗和诊断成像提供细胞外囊泡

细胞外囊泡(Extracellular vesicles, EVs)是一种由细胞释放的纳米囊泡，可以有效地交换生物信息，作为一种药物传递系统越来越受到人们的关注。然而，与脂质体类似，它们表现出较短的血液循环时间，并在肝脏和脾脏中积聚。因此，对于组织特异性递送，EV表面必须功能化。我们提出了一个基于亲和素-生物素系统的目标特异性配体灵活修饰电动汽车的新平台。利用糖基磷脂酰肌醇锚定亲和素(GPI-Av)构建供体细胞的基因工程，可以分离出表面显示亲和素的ev，并与任何生物素化配体功能化。为了验证概念，GPI-Av ev被i)生物素化抗体或ii)从头设计和合成结合碳酸酐酶IX (CAIX)的生物素化配体修饰，CAIX是一种在癌症中过度表达的膜相关酶。功能化的电动汽车被表达caix的细胞特异性结合和摄取，证明了该系统制备电动汽车用于细胞特异性药物递送的能力。

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来源期刊

Nanomedicine: Nanotechnology, Biology and Medicine 医学-纳米科技

CiteScore

8.10

自引率

3.60%

发文量

104

审稿时长

4.6 months

期刊介绍： Nanomedicine: Nanotechnology, Biology and Medicine (NBM) is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.