🤖 AI Summary
Current bio-nanotechnology (BNT) systems suffer from high cytotoxicity, limited autonomy, and reliance on genetic engineering—posing significant safety and metabolic risks. To address these challenges, this work introduces non-genetic cellular surface engineering (NG-CSE), a novel paradigm that enables transient, reversible modification of live cell membranes to construct “living BNTs” with enhanced biocompatibility and programmability while circumventing genomic editing risks. Leveraging synthetic molecular machines, NG-CSE dynamically reprograms cellular sensing, intercellular communication, and effector functions, enabling cross-species interaction and adaptive network formation. We demonstrate two innovative Internet-of-Bio-Nano-Things (IoBNT) architectures: (i) a circulating sentinel network composed of cell-based agents for liquid biopsy and real-time health monitoring; and (ii) an in vitro biological computer for bio–information fusion computing. These advances establish a foundation for safe, scalable, and intelligent biohybrid systems.
📝 Abstract
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.