Potential of the coordinated actions of multiple protein-based micromachines for medical applications.
Potential of the coordinated actions of multiple protein-based micromachines for medical applications.
复制标题
多个基于蛋白质的微型机器在医疗应用中协调行动的潜力。
DOI：
10.1021/acsami.2c08223
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发表时间：
2022
影响因子：
9.5
通讯作者：
Akiko Inagaki
中科院分区：
文献类型：
--
作者：
Hironori Yamazoe;Takaaki Kurinomaru;Akiko Inagaki
不受束缚的移动微型机器在开发有效和微创治疗方面具有很大的前景。尽管在过去的几十年里，针对特定应用开发了各种医疗微机器，但具有不同功能的多台机器的协调作用在很大程度上仍未被探索。在这项研究中，我们使用蛋白质创造了三种类型的生物相容性微型机器，并展示了它们在医疗应用中的协同作用的潜力。作为概念的证明，我们展示了神经替代疗法，通过使用抗癌前药和第一台含有酶的机器来杀死神经母细胞瘤，使前药转化为细胞毒性药物。随后，将另一台由细胞外基质组成的机器放置在死亡的癌细胞上，为细胞粘附提供合适的环境，然后使用第三台机器将胚胎干细胞（ES）和促进干细胞神经分化的基质细胞粘附在其上，并将细胞以所需的模式递送到目标位置。结果，神经母细胞瘤被来自胚胎干细胞的新型健康神经元取代，这是由多个基于蛋白质的机器组成的。我们相信，这项工作突出了异质机器群体在医疗方面的潜力，以及由蛋白质制成的高度生物相容性和功能性微机器的实用性，代表了构建更复杂的基于微机器的治疗方法的重要一步。
Untethered mobile micromachines hold great promise in the development of effective and minimally invasive therapies. Although diverse medical micromachines for specific applications have been developed over the past few decades, the coordinated action of multiple machines with different functions remains largely unexplored. In this study, we created three types of biocompatible micromachines using proteins and demonstrated the potential of their coordinated action for medical applications. As a proof of concept, we demonstrated neural replacement therapy, in which neuroblastomas were killed by using an anticancer prodrug and the first machine that contains enzymes, enabling the conversion of the prodrug into a cytotoxic drug. Subsequently, a second machine composed of extracellular matrix was placed on the dead cancer cells to provide a suitable environment for cell adhesion, on which embryonic stem (ES) cells and stromal cells that promote neural differentiation of stem cells were attached by using third machines capable of delivering cells to target positions with desired patterns. As a result, neuroblastomas were replaced with novel healthy neurons derived from ES cells by teaming multiple protein-based machines. We believe that this work highlights the potential of heterogeneous machine groups for medical treatment and the utility of highly biocompatible and functional micromachines made from proteins, representing an important step forward in building more sophisticated micromachine-based therapies.