Einfalt Tomaž, Garni Martina, Witzigmann Dominik, Sieber Sandro, Baltisberger Niklaus, Huwyler Jörg, Meier Wolfgang, Palivan Cornelia G
Department of Chemistry University of Basel Mattenstrasse 24a, BPR 1096, P.O. Box 3350 CH-4002 Basel Switzerland.
Department of Pharmaceutical Sciences Division of Pharmaceutical Technology University of Basel Klingelbergstrasse 50 CH-4056 Basel Switzerland.
Adv Sci (Weinh). 2020 Jan 9;7(4):1901923. doi: 10.1002/advs.201901923. eCollection 2020 Feb.
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.
尽管医学领域存在巨大需求且进行了大量研发工作，但迄今为止，人工细胞的组成和功能仍很有限。虽然一些人工细胞已被证明在生产治疗药物或进行体外特定反应方面取得了成功，但尚未在体内进行研究，以确定它们在避免毒性的同时是否能保持其结构和功能。在此，通过用纳米级人工细胞器（AO）补充源自供体细胞的巨型质膜囊泡，克服了这些限制，并实现了可定制的细胞模拟物——分子工厂（MF）。MF继承了供体细胞的天然细胞质和膜，而AO容纳反应性成分并提供类似细胞的结构和功能。结果表明，由于MF组成中前所未有的复杂程度，AO内部的反应在接近自然的环境中发生。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明显的毒性，并保持其完整性和功能。高度多样化的组成、多隔室化结构以及在体内保留功能的独特优势，为从在类似细胞的强大环境中研究生物相关过程到生产特定生物活性化合物等新的生物学途径开辟了道路。
