Bioinspired Molecular Factories with Architecture and In Vivo Functionalities as Cell Mimics
Bioinspired Molecular Factories with Architecture and In Vivo Functionalities as Cell Mimics
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DOI：
10.1002/advs.201901923
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发表时间：
2020-01-09
期刊：
影响因子：
15.1
通讯作者：
Palivan, Cornelia G.
中科院分区：
文献类型：
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作者：
Einfalt, Tomaz;Garni, Martina;Palivan, Cornelia G.
尽管在医学领域有巨大的需求和重大的开发努力，但迄今为止人工细胞的组成和功能有限。尽管一些人工细胞已被证明成功地用于生产治疗剂或进行体外特异性反应，但它们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，这些限制被克服，并可定制的细胞模拟物被命名为分子工厂（MFs）-通过补充来自供体细胞的巨大质膜囊泡与纳米尺寸的人工细胞器（AO）。MF继承供体细胞的天然细胞质和膜，而AO容纳反应性组分并提供细胞样结构和功能。它表明，AO内的反应发生在一个接近自然的环境中，由于前所未有的复杂程度的组成的MF。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，并保留了它们的完整性和功能。高度变化的组合物，多区室化的架构，并保存在体内的功能性的独特优势，开辟了新的生物学途径，从强大的细胞样环境中的生物相关过程的研究，以生产特定的生物活性化合物。
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.