Smart Nanomaterials and Natural Biologics for Innate-Adaptive Immune Reprogramming: A Nanobiotechnology Framework for Translational Medicine.

The innate-adaptive immune interface is a decisive control point determining whether therapeutic interventions induce durable protection, antitumor immunity, inflammatory, or immune tolerance. Many immunotherapies fail in translation because immunity is often treated as a single-output system rather than a spatially and temporally organized network shaped by tissue context, antigen-presenting cell fate, biomolecular conditioning, and metabolic state. This review introduces the immunoscape framework as a nanobiotechnology-oriented model for linking immune-state mapping with controllable translational variables, including delivery route, release kinetics, first-contact immune cells, lymphatic routing, biomolecular corona identity, antigen-presenting cell fate, and safety-gate assessment. Unlike systems immunology, which primarily describes immune networks, or conventional immune engineering, which often focuses on selected payloads, targets, or platforms, the immunoscape framework provides a design layer for predicting context-dependent immune outcomes. We discuss two converging strategies for reprogramming this interface: natural biologics, including beta-glucans, polyphenols, microbial metabolites, and extracellular vesicles; and smart nanomaterials, including lipid nanoparticles, biomimetic vesicles, lymph node-targeted platforms, and stimulus-responsive nanoarchitectures. We further propose translational design rules to guide clinically realistic immune-reprogramming nanomedicines for cancer, infectious, inflammatory, and regenerative applications.