Optically Active Bionanomachine Interfaces Build Therapeutic Nanonetworks for Glioblastoma Multiforme

Avraam El Hamidieh, Nikolaos Dietis, A. Samoylenko, I. Meiser, Niovi Nicolaou, Eslam Abdelrady, A. Zhyvolozhnyi, S. Vainio, A. Odysseos
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Abstract

The evolution of Glioblastoma Multiforme (GBM) is defined by the dynamics of growing bionanomachine networks in an interplay between "senders" or "transceivers" and "receivers". Central to this process are the inter-communications between sub-cellular bionanomachines secreted by GBM cells in the form of exosomes. Herein we present a dynamic cell-based therapeutic nanonetwork of genetically engineered optically active bionanomachines. The communication paradigm is defined by the interaction between neural stem cell-derived exosomes expressing Enhanced Green Fluorescent Protein and GBM cells expressing Tandem Dimer Tomato protein (tdT), based on the dynamic transfer of energies of excited state bionanomachines in resonance. With EGFP serving as energy donor and tdT as energy acceptor we provide multilevel evidence validating a Förster Resonance Energy Transfer - mediated interaction between GBM cells and exosomes, therefore documenting their sustainable and close proximity. Such an approach has the potential to enable wireless communication between optically active bionanomachines via quantifiable interfaces within channel networks, further enabling mechanistic and therapeutic models.
光学活性生物机器界面构建多形性胶质母细胞瘤治疗性纳米网络
多形性胶质母细胞瘤(GBM)的进化是由在“发送者”或“收发者”和“接收者”之间相互作用的不断增长的生物神经网络的动力学所定义的。这一过程的核心是由GBM细胞以外泌体的形式分泌的亚细胞生物异常机器之间的相互通信。在这里,我们提出了一个动态的基于细胞的治疗纳米网络的基因工程光学活性生物机器。这种通讯模式是由表达增强型绿色荧光蛋白的神经干细胞衍生外泌体和表达串联二聚体番茄蛋白(tdT)的GBM细胞之间的相互作用所定义的,这种相互作用基于激发态生物异常机器在共振中的能量动态转移。EGFP作为能量供体,tdT作为能量受体,我们提供了多层次的证据,验证了Förster共振能量转移介导的GBM细胞和外泌体之间的相互作用,因此记录了它们的持续和密切的关系。这种方法有可能通过通道网络中的可量化接口实现光活性生物机器之间的无线通信,进一步实现机制和治疗模型。
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