Oral antioxidant therapy for Inflammatory Bowel Disease (IBD) is currently hampered by the “oral delivery paradox”, wherein the therapeutic potential of bioactive agents is compromised by poor aqueous solubility and rapid gastrointestinal washout. To overcome these biopharmaceutical barriers, we engineered a bio-inspired theranostic platform (QUE@SP) via the electrostatic anchoring of cationic, quercetin-loaded zein/chitosan nanoparticles onto the surface of the natural helical microcarrier, Spirulina platensis (SP). Mechanistically, the biomimetic helical morphology of SP induces a hydrodynamic locking effect within the intestinal villi, transforming the transient transit of nanoparticles into a sustained mucosal depot. Following mucosal attachment, the controlled release of quercetin is driven by microbiota-triggered enzymatic degradation of the chitosan-zein matrix, ensuring site-specific drug discharge. In vivo evaluations demonstrated a prolonged colonic retention of up to 48 hours, which maximized localized drug exposure. This translated into potent reactive oxygen species (ROS) scavenging, macrophage polarization, and the restoration of intestinal barrier integrity in colitis murine models. Furthermore, as an inherently biocompatible carrier, SP facilitated self-trackable monitoring of mucosal distribution via its intrinsic fluorescence, followed by complete biodegradation and nutritional absorption. Ultimately, this work introduces a shape-driven paradigm that repurposes natural microalgae into a precision oral vehicle, providing a biologically integrated strategy for targeted colitis therapy.

Crohn’s disease (CD) is chronic inflammatory bowel disorder characterized by transmural inflammation, intestinal barrier disruption, and gut microbiota dysbiosis. Although probiotics show therapeutic potential for CD through modulating the intestinal flora, conventional oral formulations are constrained by low survival rates in the gastrointestinal tract and limited efficacy. Inspired by the metal-coordinating property and anti-inflammatory effect of baicalin (BA), the nanoengineered probiotics Fe-BT@EcN are developed through synergy with tannic acid and ferric ions, demonstrating enhanced resistance to adverse gastric environment as well as improved intestinal adhesion and colonization. Notably, as confirmed by network pharmacology and molecular docking studies, BA targets dual therapeutic pathways in CD intervention to elevate antioxidant and anti-inflammatory activities through regulation of reactive oxygen species (ROS) levels and inhibition of the IL-6/STAT3 signaling pathway. In a murine 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced CD model, Fe-BT@EcN exhibited synergistic therapeutic efficacy by alleviating colonic inflammation, restoring epithelial barrier function, and reestablishing microbial homeostasis. This study provides a feasible strategy to develop multifunctional oral microecologics for CD treatment through leveraging different probiotics and natural bioactive small molecules.

The emergence of human coronaviruses (HCoVs), especially the current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), engender severe threats to public health globally. Despite the outstanding breakthrough of new vaccines and therapeutic medicines in the past years, HCoVs still undergo unpredictable mutations, thus demanding more effective diagnostic and therapeutic strategies. Benefitting from the unique physicochemical properties and multiple nano–bio interactions, nanomaterials hold promising potential to fight against various HCoVs, either by providing sensitive and economic nanosensors for rapid viral detection, or by developing translatable nanovaccines and broad-spectrum nanomedicines for HCoV treatment. Herein, we systemically summarized the recent applications of nanoagents in diagnostics and therapeutics for HCoV-induced diseases, as well as their limitations and perspectives against HCoV variants. We believe this review will promote the design of innovative theranostic nanoagents for the current and future HCoV-caused pandemics.