Stimuli-Responsive Biomolecular Materials for Targeted Delivery and Local Therapeutic Action in Disease Microenvironments

Disease microenvironments exhibit defining biochemical and biophysical cues, such as altered pH, enzyme activity, redox stress, hypoxia, and microbiome-derived signals, that can be leveraged to achieve selective therapeutic action at the site of disease. Stimuli-responsive biomolecular materials assembled from proteins, peptides, and nucleic acids are particularly well suited to this challenge because their sequences, architectures, and interfaces can be programmed with molecular precision. Recent advances in supramolecular assembly, sequence-defined design, and biointerface engineering are enabling materials that localise, activate, and release therapeutics with improved control and interpretability. At the same time, the field benefits from rigorous structure–property–function studies and translation-enabling engineering (reproducibility, stability, and scalable manufacture) grounded in non-clinical evidence rather than clinical outcome claims.This Research Topic aims to consolidate advances in stimuli-responsive biomolecular materials for targeted delivery and local therapy in disease-relevant microenvironments. We welcome contributions that explain how specific molecular design choices (sequence and chemistry, valency, topology, assembly pathway, and biointerface functionalization) govern emergent material properties such as architecture, mechanics, transport, degradation, and interfacial behaviour. A central emphasis is on mechanistic insight into how these properties determine delivery-relevant performance, including localisation/retention, activation thresholds, release kinetics, biodistribution-relevant behaviour, cellular uptake, and biointeractions (e.g., immune recognition, protein corona, mucus penetration, microbiome interactions). Suitable application contexts include cancer, inflammation, infection, and oral/periodontal conditions, provided that the primary novelty lies in the biomolecular material design and stimulus-coupled delivery/therapeutic function.Submissions should prioritise non-clinical, mechanism-forward evidence supported by rigorous physicochemical characterisation and validation in in vitro, ex vivo, and relevant preclinical models (including organoids and organ-on-a-chip). Studies may include nano/microcarriers or local depots for biologics (proteins, peptides, nucleic acids), and hybrid systems where biomacromolecules are central to stimulus response and interface design. Imaging, sensing, or reporter functions are in scope only when they enable mechanistic readouts of targeting, activation, or release within the delivery/therapy system (not stand-alone diagnostics or device development). We also encourage translation-enabling engineering, including reproducible fabrication, batch consistency, critical quality attributes, storage stability, and biosafety-by-design. Clinical trials, clinical cohorts, and clinical efficacy claims are out of scope. Topic editors: Xinglu Jiang, Zhenqiang Ning, Hongfei Jiang Source: https://www.frontiersin.org/research-topics/78132/stimuli-responsive-biomolecular-materials-for-targeted-delivery-and-local-therapeutic-action-in-disease-microenvironments