Programmable DNA Nanocages Enable Adaptive Spatiotemporal Organization of Biomimetic Organelle Networks

Abstract Synthetic organelles have emerged to simulate the multicompartmental organization and communication within cells. However, current synthetic organelles (e.g., lipid vesicles and polymer‐based assemblies) often suffer from insufficient structural stability and lack adaptive feedback mechanisms due to the absence of support and dynamic regulation by natural cytoskeletal proteins, which limits the construction of autonomous communication networks. Here, we present a modular and programmable DNA nanocage strategy for constructing stable and adaptive synthetic organelle networks. Using extracellular vesicles (EVs) as a model, we anchored tetrahedral DNA frameworks (TDNs) on the EV surface and assembled a mechanically reinforced biomimetic DNA nanocage via palindromic hybridization chain reaction (PHCR), thereby significantly enhancing vesicle stability and effectively preventing membrane fusion upon contact. The modular design enables the integration of logic‐gated DNA elements as dynamic contact sites, allowing environment‐responsive reconfiguration of inter‐artificial‐organelle spatial organization and signaling. This work provides a customizable platform for constructing artificial organelles with adaptive feedback regulation, offering broad potential in synthetic biology, biomedical applications, and smart material design.