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仿生原代细胞具有巨噬细胞样捕获和消化蛋白病原体的特性。

Biomimetic Protocells Featuring Macrophage-Like Capture and Digestion of Protein Pathogens.

机构信息

Leibniz-Institut für Polymerforschung Dresden e.V., D-01069, Dresden, Germany.

Organic Chemistry of Polymers, Technische Universität Dresden, D-01062, Dresden, Germany.

出版信息

Small Methods. 2023 Dec;7(12):e2300257. doi: 10.1002/smtd.202300257. Epub 2023 Aug 20.

Abstract

Modern medical research develops interest in sophisticated artificial nano- and microdevices for future treatment of human diseases related to biological dysfunctions. This covers the design of protocells capable of mimicking the structure and functionality of eukaryotic cells. The authors use artificial organelles based on trypsin-loaded pH-sensitive polymeric vesicles to provide macrophage-like digestive functions under physiological conditions. Herein, an artificial cell is established where digestive artificial organelles (nanosize) are integrated into a protocell (microsize). With this method, mimicking crossing of different biological barriers, capture of model protein pathogens, and compartmentalized digestive function are possible. This allows the integration of different components (e.g., dextran as stabilizing block) and the diffusion of pathogens in simulated cytosolic environment under physiological conditions. An integrated characterization approach is carried out, with identifying electrospray ionization mass spectrometry as an excellent detection method for the degradation of a small peptide such as β-amyloid. The degradation of model enzymes is measured by enzyme activity assays. This work is an important contribution to effective biomimicry with the design of cell-like functions having potential for therapeutic action.

摘要

现代医学研究对用于治疗与生物功能障碍相关的人类疾病的复杂人工纳米和微设备产生了兴趣。这包括设计能够模拟真核细胞结构和功能的原细胞。作者使用基于负载胰蛋白酶的 pH 敏感聚合物囊泡的人工细胞器,在生理条件下提供类似于巨噬细胞的消化功能。在此,建立了一种人工细胞,其中将消化用人工细胞器(纳米尺寸)集成到原细胞(微尺寸)中。通过这种方法,可以模拟不同生物屏障的穿越、模型蛋白病原体的捕获和分隔的消化功能。这允许不同组件(例如,葡聚糖作为稳定块)的集成以及在生理条件下模拟细胞溶质环境中病原体的扩散。进行了一种集成的表征方法,确定电喷雾电离质谱法是检测小肽(如β-淀粉样蛋白)降解的一种极好方法。通过酶活性测定来测量模型酶的降解。这项工作是对具有治疗作用的细胞样功能的有效仿生设计的重要贡献。

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