标题： 通过表面工程劫持活细胞用于生物纳米事物的互联网 显示英文标题

标题： Hijacking Living Cells with Surface Engineering for the Internet of Bio-Nano Things

摘要： 互联网生物纳米事物（IoBNT）有望通过在前所未有的分辨率下将网络领域与生命系统相连接，彻底改变医疗保健。 实现这一愿景取决于生物纳米事物（BNTs）的发展，即能够在生物环境中进行感知、执行和通信的功能节点。 现有的BNT架构，例如基于纳米材料、生物合成和被动分子代理的架构，面临重大限制，包括毒性、缺乏自主性，或与基因改造相关的安全性和代谢负担。 本文提出一个第四范式：通过非基因细胞表面工程（NG-CSE）暂时劫持活细胞，以实现活体BNT。 NG-CSE允许通过合成分子机器对细胞膜进行精确且可逆的功能化，重新编程细胞功能和相互作用，而无需改变基因组。 它独特地结合了活细胞的固有生物相容性和自主性，以及纳米技术带来的可编程性，降低了基因工程的风险。 我们批判性地回顾了NG-CSE的工具箱，并探讨了它为IoBNT所带来的机遇，包括可编程的细胞间通信、动态网络拓扑和改进的生物-网络接口。 此外，我们提出了利用这些能力的新IoBNT架构，例如利用细胞自主性的循环哨兵网络，用于连续液体活检，以及合理设计的体外生物计算机，利用跨王国相互作用。 我们还概述了使用NG-CSE建模和利用细胞自主性的关键挑战，并为在IoBNT中有效利用NG-CSE增强的活体BNT提供了一条路线图。 显示英文摘要

摘要： The Internet of Bio-Nano Things (IoBNT) promises to revolutionize healthcare by interfacing the cyber domain with the living systems at unprecedented resolution. Realizing this vision hinges on the development of Bio-Nano Things (BNTs), i.e., functional nodes capable of sensing, actuation, and communications within biological environments. Existing BNT architectures, e.g., nanomaterial-based, biosynthetic, and passive molecular agents, face significant limitations, including toxicity, lack of autonomy, or the safety and metabolic burdens associated with genetic modification. This paper posits a fourth paradigm: the transient hijacking of living cells via non-genetic cell surface engineering (NG-CSE) to enable living BNTs. NGCSE allows for the precise, reversible functionalization of cell membranes with synthetic molecular machinery, reprogramming cellular functions and interactions without altering the genome. It uniquely combines the inherent biocompatibility and agency of living cells with the programmability enabled by nanotechnology, mitigating the risks of genetic engineering. We critically review the toolbox of NG-CSE and explore the opportunities it unlocks for IoBNT, including programmable cell-cell communication, dynamic network topologies, and improved bio-cyber interfacing. Moreover, we propose novel IoBNT architectures that leverage these capabilities, such as circulating sentinel networks exploiting cellular agency for continuous liquid biopsy, and rationally designed, in vitro biocomputers exploiting interkingdom interactions. We also outline the critical challenges in modeling and exploiting cellular agency with NG-CSE, providing a roadmap for the effective utilization of NG-CSE-enabled living BNTs within IoBNT.