Programmable Biointerfaces and Adaptive Functionality in Next-Generation Green Nanomaterials.

Recent advances in green nanomaterials have primarily focused on mitigating toxicity through passive approaches, yet emerging technologies suggest a transformative paradigm shift toward programmable nanomaterials with dynamic biointerfaces. This Review explores how convergent innovations in synthetic biology, DNA nanotechnology, artificial intelligence, and advanced manufacturing are creating unprecedented opportunities for developing nanomaterials with context-responsive functionality. Integration of cell-free synthetic biology enables nanomaterials with genetic-circuit-driven responses to biological cues, allowing expression of bioactive compounds precisely when and where needed. DNA nanotechnology provides molecular-level programmability through stimuli-responsive structures that can perform logical operations based on complex biological inputs. Advanced machine learning approaches are revolutionizing predictive design by identifying nonintuitive correlations between green synthesis parameters and programmable functionalities. Metabolic engineering approaches utilizing engineered microbial systems offer unprecedented control over nanomaterial synthesis with reduced batch-to-batch variability, while 4D bioprinting enables macroscale assemblies with nanoscale programmable elements distributed in precise spatiotemporal arrangements. These converging technologies are enabling the development of autonomous theranostic systems with closed-loop functionality, capable of sensing biological parameters, processing this information through molecular computing, and adjusting therapeutic activity accordingly. This evolution represents a fundamental reconceptualization of biocompatibility from a static property to a dynamic, programmable characteristic, potentially yielding nanomaterials that behave more like sophisticated biological entities than traditional therapeutic agents. While significant challenges remain in stability, sensitivity, and manufacturing scalability, this emerging paradigm promises transformative advances in precision nanomedicine through self-regulating, patient-responsive therapeutic systems.