Double-layer probiotic encapsulation for enhanced bacteriotherapy against inflammatory bowel disease

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.

Nano-STING agonist-decorated microrobots boost innate and adaptive anti-tumor immunity

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 reactioninduced 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.

Shape-controlled synthesis of liquid metal nanodroplets for photothermal therapy

The capping agents for liquid metal (LM) nanodroplets in aqueous solutions are restricted to thiol-containing and positively-charged molecules or macromolecules.However,both thiolate-metal complex and electrostatic interaction are liable to detachment upon strong mechanical forces such as sonication,leading to limited stability and applications.To address this,we utilized ultrasmall water soluble melanin nanoparticles (MNPs) as the capping agent,which exhibited strong metal binding capability with the oxide layer of gallium based LMs and resulted in enhanced stability.Interestingly,shape-controlled synthesis of LM nanodroplets can be achieved by the incorporation of MNPs.Various EGaln nanostructures including nanorice,nanosphere and nanorod were obtained by simply tuning the feed ratio,sonication time,and suspension temperature.Among these shapes,EGaln nanorice has the best photothermal conversion efficiency,which could be leveraged for photothermal therapy.