Neutrophils have recently emerged as promising carriers for drug delivery due to their unique properties including rapid response toward inflammation,chemotaxis,and transmigration.When integrated with nanotechnology t...Neutrophils have recently emerged as promising carriers for drug delivery due to their unique properties including rapid response toward inflammation,chemotaxis,and transmigration.When integrated with nanotechnology that has enormous advantages in improving treatment efficacy and reducing side effects,neutrophil-based nano-drug delivery systems have expanded the repertoire of nanoparticles employed in precise therapeutic interventions by either coating nanoparticles with their membranes,loading nanoparticles inside living cells,or engineering chimeric antigen receptor(CAR)-neutrophils.These neutrophil-inspired therapies have shown superior biocompatibility,targeting ability,and therapeutic robustness.In this review,we summarized the benefits of combining neutrophils and nanotechnologies,the design principles and underlying mechanisms,and various applications in disease treatments.The challenges and prospects for neutrophil-based drug delivery systems were also discussed.展开更多
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 dys...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.展开更多
基金supported,in part,by METAVIVOR Foundation Early Career Research Grant Award,American Cancer Society Research Scholar Grant(Grant number:RSG-23-1140821-01-ET)the University of Wisconsin Carbone Cancer Center Research Collaborative and the Pancreas Cancer Task Force,and the start-up package from the University of Wisconsin-Madison.
文摘Neutrophils have recently emerged as promising carriers for drug delivery due to their unique properties including rapid response toward inflammation,chemotaxis,and transmigration.When integrated with nanotechnology that has enormous advantages in improving treatment efficacy and reducing side effects,neutrophil-based nano-drug delivery systems have expanded the repertoire of nanoparticles employed in precise therapeutic interventions by either coating nanoparticles with their membranes,loading nanoparticles inside living cells,or engineering chimeric antigen receptor(CAR)-neutrophils.These neutrophil-inspired therapies have shown superior biocompatibility,targeting ability,and therapeutic robustness.In this review,we summarized the benefits of combining neutrophils and nanotechnologies,the design principles and underlying mechanisms,and various applications in disease treatments.The challenges and prospects for neutrophil-based drug delivery systems were also discussed.
基金supported by the University of Wisconsin Carbone Cancer Center Research Collaborativethe Pancreas Cancer Task Force and the start-up package from the University of Wisconsin-Madison.
文摘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.
