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Bioinspired Molecular Factories with Architecture and In Vivo Functionalities as Cell Mimics.
Advanced Science ( IF 15.1 ) Pub Date : 2020-01-09 , DOI: 10.1002/advs.201901923
Tomaž Einfalt 1, 2 , Martina Garni 1 , Dominik Witzigmann 2 , Sandro Sieber 2 , Niklaus Baltisberger 1 , Jörg Huwyler 2 , Wolfgang Meier 1 , Cornelia G Palivan 1
Affiliation  

Despite huge need in the medical domain and significant development efforts, artificial cells to date have limited composition and functionality. Although some artificial cells have proven successful for producing therapeutics or performing in vitro specific reactions, they have not been investigated in vivo to determine whether they preserve their architecture and functionality while avoiding toxicity. Here, these limitations are overcome and customizable cell mimic is achieved-molecular factories (MFs)-by supplementing giant plasma membrane vesicles derived from donor cells with nanometer-sized artificial organelles (AOs). MFs inherit the donor cell's natural cytoplasm and membrane, while the AOs house reactive components and provide cell-like architecture and functionality. It is demonstrated that reactions inside AOs take place in a close-to-nature environment due to the unprecedented level of complexity in the composition of the MFs. It is further demonstrated that in a zebrafish vertebrate animal model, these cell mimics show no apparent toxicity and retain their integrity and function. The unique advantages of highly varied composition, multicompartmentalized architecture, and preserved functionality in vivo open new biological avenues ranging from the study of biorelevant processes in robust cell-like environments to the production of specific bioactive compounds.

中文翻译:

具有结构和体内功能作为细胞模拟物的生物启发分子工厂。

尽管在医学领域有巨大的需求,并且付出了巨大的努力,但迄今为止,人造细胞的成分和功能仍然有限。尽管已证明某些人造细胞可成功产生治疗剂或进行体外特异性反应,但尚未在体内进行研究以确定它们是否在避免毒性的同时保留其结构和功能。在这里,克服了这些局限,并通过向供体细胞衍生的巨大质膜囊泡补充了纳米级人工细胞器(AOs),实现了分子工厂(MF)的可定制细胞模拟。MF继承供体细胞的天然细胞质和膜,而AO容纳反应性成分并提供细胞样结构和功能。事实证明,由于MF组成中前所未有的复杂性水平,AO内部的反应是在接近自然的环境中发生的。进一步证明,在斑马鱼脊椎动物模型中,这些细胞模拟物没有表现出明显的毒性,并保持其完整性和功能。体内高度可变的组成,多隔室化的结构以及保留的体内功能的独特优势开辟了新的生物学途径,从研究健壮细胞状环境中的生物相关过程到生产特定的生物活性化合物。
更新日期:2020-01-09
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