Inflammatory bowel disease (IBD) is inflammatory intestinal disorders associated with dysregulated gut microbiota. Bacteriotherapy that leverages bacteria as therapeutics has shown tremendous promise in resolving gut dysbiosis and reducing inflammatory mediators to treat IBD. Orally delivered probiotics, such as Escherichia coli Nissle 1917 (EcN), can produce beneficial ingredients, competitively inhibit the proliferation of pathogens, and promote the restoration of gut microbiome homeostasis. However, environmental stresses (such as gastric acids) in the gastrointestinal (GI) tract pose an enormous challenge to the probiotics following oral administration, leading to decreases in viability and activity of probiotics. Meanwhile, the inferior mucoadhesive capability of probiotics results in low colonization efficacy, further compromising their therapeutic effect. Coating probiotics with functional biomaterials may protect them from elimination and prolong their retention in the GI tract. Here, we developed a facile double-layer electrostatic assembly technique to encapsulate EcN bacteria in protective layers of mucoadhesive chitosan (CS) and immunomodulatory hyaluronic acid (HA) to generate HA-CS-EcN. These biomaterials confer the coated EcN resistance to environmental assault and enhanced mucoadhesion in the GI tract. The probiotics equipped with the multifunctional shield can thus suppress inflammation and reshape the intestinal microenvironment to enhance therapeutic efficacy for the prevention and treatment of IBD. Collectively, this study presents a novel probiotic coating strategy to augment the outcome of bacteriotherapy to combat IBD.

Activating the cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of interferon genes (cGAS/STING) signaling has emerged as a promising anti-tumor strategy due to the important role of the pathway in innate and adaptive immunity, yet the selective delivery of STING agonists to tumors following systemic administration remains challenging. Herein, we develop a nano-STING agonist-decorated microrobot platform to achieve the enhanced anti-tumor effect. Fe ions and the STING agonist 2’3’-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) are co-encapsulated in the mitochondria-targeting nanoparticles (mTNPs), which can trigger the release of mitochondrial DNA (mtDNA) by Fenton reaction-induced mitochondria oxidative damage. The exogenous cGAMP and the endogenous mtDNA can work synergistically to induce potent cGAS/STING signaling activation. Furthermore, we decorate mTNPs onto Salmonella typhimurium VNP20009 (VNP) bacteria to facilitate tumor accumulation and deep penetration. We demonstrate that the systemic administration of this microrobot activates both innate and adaptive immunity, improving the immunotherapeutic efficacy of the STING agonists.