There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels,and molecular mediators directed aga...There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels,and molecular mediators directed against harmful stimuli, is closely associated with many human diseases.As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.展开更多
Introduction： Intrauterine growth restriction （IUGR） is commonly caused by placental insufficiency, resulting in a chronic hypoxic environment and subsequent abnormal fetal development. The developing brain is part...Introduction： Intrauterine growth restriction （IUGR） is commonly caused by placental insufficiency, resulting in a chronic hypoxic environment and subsequent abnormal fetal development. The developing brain is particularly vulnerable to IUGR conditions. Multiple causal factors associated with brain injury in fetal growth restriction include the timing of placental insufficiency, onset and subsequent severity of fetal compromise, fetal cerebrovascular response and the redistribution of brain blood flow. Although a significant proportion of IUGR infants exhibit adverse long-term neu- rological outcomes, relatively few studies have focused on the mechanisms of brain injury in the IUGR neonate. Clini- cal imaging studies of IUGR infants demonstrate alterations in grey matter and white matter volume and structure （Tolsa et al., 2004; Esteban et al., 2010; Padilla et al., 2015）. Cortical grey matter volume is reduced by up to 28% compared with control infants （Tolsa et al., 2004） and both white and grey matter show structural changes （Esteban et al., 2010）. These structural changes persist at 1 year of age and are associated with significant developmental disabilities （Tolsa et al., 2004;展开更多
Immune effector mechanisms play key roles in the progressive（secondary）neurodegenerative changes that follow spinal cord injury（SCI）.In our recent paper（Brennan et al.,2015）,we showed that the inflammatory respo...Immune effector mechanisms play key roles in the progressive（secondary）neurodegenerative changes that follow spinal cord injury（SCI）.In our recent paper（Brennan et al.,2015）,we showed that the inflammatory response to SCI includes rapid and robust activation of the innate immune complement system, with tissue levels of complement component 5a （C5a - an activation product generated by the proteolysis of complement factor 5 （C5）） peaking 12 to 24 hours post-iniurv.展开更多
In rheumatoid arthritis(RA),the presence of substantial inflammatory macrophages and osteoclasts in joints is known to contribute to the progression of articular inflammation and bone destruction.Herein,we develop a s...In rheumatoid arthritis(RA),the presence of substantial inflammatory macrophages and osteoclasts in joints is known to contribute to the progression of articular inflammation and bone destruction.Herein,we develop a sialic acid-modified tetra malonic acid derivative of C70 fullerene(STMF).STMF possesses inflammation-targeting capability that can effectively impede the differentiation of macrophages and osteoclasts,offering a potential treatment strategy for RA.STMF acts as a mimic of sialyl Lewis x,enabling it to specifically bind with E-selectin,which is overexpressed on inflamed endothelial cells.This selective binding results in a targeted distribution of STMF to inflamed joints,addressing articular in-flammation.Upon uptake by macrophages,STMF demonstrates the ability to effectively eliminate intracellular reactive oxygen species and deactivate the downstream events,thereby suppressing their differentiation into M1-phenotype and osteoclastogenesis.In our experiments using collagen-induced arthritis mouse models,STMF significantly improves paw swelling and redness,mitigates articular inflammation with reduced M1 macrophages,lessens osteoclasts,and repairs bone erosion with neglectable side effects.These findings suggest that STMF has potential as a therapeutic agent for RA,leveraging inflammation-targeting fullerene nanomaterials.展开更多
White blood cells(WBCs)play essential roles against inflammatory disorders,bacterial infections,and cancers.Inspired by nature,WBC membrane-camouflaged nanocarriers(WBC-NCs)have been developed to mimic the“dynamic”f...White blood cells(WBCs)play essential roles against inflammatory disorders,bacterial infections,and cancers.Inspired by nature,WBC membrane-camouflaged nanocarriers(WBC-NCs)have been developed to mimic the“dynamic”functions of WBCs,such as transendothelial migration,adhesion to injured blood vessels,etc,which make them promising for diverse medical applications.WBC-NCs inherit the cell membrane antigens of WBCs,while still exhibiting the robust inflammation-related therapeutic potential of synthetic nanocarriers with excellent(bio)physicochemical performance.This review summarizes the proposed concept of cell membrane engineering,which utilizes physical engineering,chemical modification,and biological functionalization technologies to endow the natural cell membrane with abundant functionalities.In addition,it highlights the recent progress and applications of WBC-NCs for inflammation targeting,biological neutralization,and immune modulation.Finally,the challenges and opportunities in realizing the full potential of WBC-NCs for the manipulation of inflammation-related therapeutics are discussed.展开更多
Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by synovitis and destruction of cartilage,promoted by sustained inflammation.However,current treatments remain unsatisfactory due to lacking of s...Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by synovitis and destruction of cartilage,promoted by sustained inflammation.However,current treatments remain unsatisfactory due to lacking of selective and effective strategies for alleviating inflammatory environments in RA joint.Inspired by neutrophil chemotaxis for inflammatory region,we therefore developed neutrophil-derived exosomes functionalized with sub-5 nm ultrasmall Prussian blue nanoparticles(uPB-Exo)via click chemistry,inheriting neutrophil-targeted biological molecules and owning excellent anti-inflammatory properties.uPB-Exo can selectively accumulate in activated fibroblast-like synoviocytes,subsequently neutralizing pro-inflammatory factors,scavenging reactive oxygen species,and alleviating inflammatory stress.In addition,uPB-Exo effectively targeted to inflammatory synovitis,penetrated deeply into the cartilage and real-time visualized inflamed joint through MRI system,leading to precise diagnosis of RA in vivo with high sensitivity and specificity.Particularly,uPB-Exo induced a cascade of anti-inflammatory events via Th17/Treg cell balance regulation,thereby significantly ameliorating joint damage.Therefore,nanoenzyme functionalized exosomes hold the great potential for enhanced treatment of RA in clinic.展开更多
Neuroinflammation is one of the three important pathological features in neurodegenerative diseases including Parkinson’s disease(PD).The regulation of neuroinflammation can reduce the severity of neurological damage...Neuroinflammation is one of the three important pathological features in neurodegenerative diseases including Parkinson’s disease(PD).The regulation of neuroinflammation can reduce the severity of neurological damage to alleviate diseases.Numerous studies have shown that the phenotype switch of microglia is tightly associated with the nuclear factorκB(NF-κB)-mediated inflammatory pathway.Therefore,the small interfering RNA(siRNA)therapy for downregulating the expression of NF-κB,provides a promising therapeutic strategy for Parkinson’s disease treatments.Considering the brain delivery challenges of siRNA,a sequential targeting inflammation regulation(STIR)delivery system based on poly(amino acid)s is developed to improve the therapeutic effects of Parkinson’s disease treatments.The STIR system sequentially targets the blood–brain barrier and the microglia to enhance the effective concentration of siRNA in the targeted microglia.The results demonstrate that the STIR nanoparticles can transform microglial phenotypes and regulate brain inflammation,thus achieving neuronal recovery and abnormal aggregation ofα-synuclein protein(α-syn)reduction in the treatment of Parkinson’s disease.Herein,this STIR delivery system provides a promising therapeutic platform in PD treatments and has great potential for other neurodegenerative diseases’therapies.展开更多
基金supported by the National Natural Science Foundation of China (81472757, 81773283, 81361140344, 81600175 and 81671815)the National Basic Research Program of China (973 Program, 2013CB932502)
文摘There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels,and molecular mediators directed against harmful stimuli, is closely associated with many human diseases.As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.
基金supported by the University of Queensland Medicine and Biomedical Sciences Emerging Leaders grant and Royal Brisbane and Women’s Hospital Foundation research grant
文摘Introduction： Intrauterine growth restriction （IUGR） is commonly caused by placental insufficiency, resulting in a chronic hypoxic environment and subsequent abnormal fetal development. The developing brain is particularly vulnerable to IUGR conditions. Multiple causal factors associated with brain injury in fetal growth restriction include the timing of placental insufficiency, onset and subsequent severity of fetal compromise, fetal cerebrovascular response and the redistribution of brain blood flow. Although a significant proportion of IUGR infants exhibit adverse long-term neu- rological outcomes, relatively few studies have focused on the mechanisms of brain injury in the IUGR neonate. Clini- cal imaging studies of IUGR infants demonstrate alterations in grey matter and white matter volume and structure （Tolsa et al., 2004; Esteban et al., 2010; Padilla et al., 2015）. Cortical grey matter volume is reduced by up to 28% compared with control infants （Tolsa et al., 2004） and both white and grey matter show structural changes （Esteban et al., 2010）. These structural changes persist at 1 year of age and are associated with significant developmental disabilities （Tolsa et al., 2004;
基金supported by Spinal Cure Australia(Career Development Fellowship to MJR),The University of Queensland,and the National Health and Medical Research Council of Australia(Project Grant 1060538 to MJR)
文摘Immune effector mechanisms play key roles in the progressive（secondary）neurodegenerative changes that follow spinal cord injury（SCI）.In our recent paper（Brennan et al.,2015）,we showed that the inflammatory response to SCI includes rapid and robust activation of the innate immune complement system, with tissue levels of complement component 5a （C5a - an activation product generated by the proteolysis of complement factor 5 （C5）） peaking 12 to 24 hours post-iniurv.
基金supported by the National Natural Science Foundation of China(grant no.52272048)the Beijing Natural Science Foundation(grant no.2222090)+1 种基金the Ministry of Science and Technology of China(grant no.2022YFA1205900),the Key Research Program of the Chinese Academy of Sciences(grant no.QYKJZD-SSW-SLH01)Natural Science Foundation of Shandong Province(grant no.ZR2020QB016).
文摘In rheumatoid arthritis(RA),the presence of substantial inflammatory macrophages and osteoclasts in joints is known to contribute to the progression of articular inflammation and bone destruction.Herein,we develop a sialic acid-modified tetra malonic acid derivative of C70 fullerene(STMF).STMF possesses inflammation-targeting capability that can effectively impede the differentiation of macrophages and osteoclasts,offering a potential treatment strategy for RA.STMF acts as a mimic of sialyl Lewis x,enabling it to specifically bind with E-selectin,which is overexpressed on inflamed endothelial cells.This selective binding results in a targeted distribution of STMF to inflamed joints,addressing articular in-flammation.Upon uptake by macrophages,STMF demonstrates the ability to effectively eliminate intracellular reactive oxygen species and deactivate the downstream events,thereby suppressing their differentiation into M1-phenotype and osteoclastogenesis.In our experiments using collagen-induced arthritis mouse models,STMF significantly improves paw swelling and redness,mitigates articular inflammation with reduced M1 macrophages,lessens osteoclasts,and repairs bone erosion with neglectable side effects.These findings suggest that STMF has potential as a therapeutic agent for RA,leveraging inflammation-targeting fullerene nanomaterials.
基金The authors are very grateful for the financial support by National Natural Science Foundation of China(Grant No.31900957)Shandong Provincial Natural Science Foundation(Grant No.ZR2019QC007)+4 种基金Innovation and technology program for the excellent youth scholars of higher education of Shandong province(Grant No.2019KJE015)Traditional Chinese Medicine Science and Technology Project of Shandong province(Grant No.2021Q069)Open Fund of Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid(Grant No.KTRDHA-Y201902)National College Students Innovation and Entrepreneurship Training Program of China(Grant No.S202011065041,202211065038)Zhejiang Engineering Research Center for Tissue Repair Materials(Grant No:WIUCASZZXF21004).
文摘White blood cells(WBCs)play essential roles against inflammatory disorders,bacterial infections,and cancers.Inspired by nature,WBC membrane-camouflaged nanocarriers(WBC-NCs)have been developed to mimic the“dynamic”functions of WBCs,such as transendothelial migration,adhesion to injured blood vessels,etc,which make them promising for diverse medical applications.WBC-NCs inherit the cell membrane antigens of WBCs,while still exhibiting the robust inflammation-related therapeutic potential of synthetic nanocarriers with excellent(bio)physicochemical performance.This review summarizes the proposed concept of cell membrane engineering,which utilizes physical engineering,chemical modification,and biological functionalization technologies to endow the natural cell membrane with abundant functionalities.In addition,it highlights the recent progress and applications of WBC-NCs for inflammation targeting,biological neutralization,and immune modulation.Finally,the challenges and opportunities in realizing the full potential of WBC-NCs for the manipulation of inflammation-related therapeutics are discussed.
基金Key Program of NSFC(81730067)Major Project of NSFC(81991514)+5 种基金Fundamental Research Funds for the Central Universities(14380493,14380494)National Science Foundation of China(Grant No 82002370,31800806,82000069)China Postdoctoral Science Foundation(Grant No 2019M661806)Natural science foundation of Jiangsu province(Grant No BK20200117,BK20200314),Jiangsu postdoctoral research support project(Grant No 2021K059A)Nanjing University Innovation Program for PhD candidates(CXYJ21-62)Jiangsu Provincial Key Medical Center Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Medical Youth Talent Foundation,Jiangsu Provincial Key Medical Talent Foundation,Program of Innovation and Entrepreneurship of Jiangsu Province.
文摘Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by synovitis and destruction of cartilage,promoted by sustained inflammation.However,current treatments remain unsatisfactory due to lacking of selective and effective strategies for alleviating inflammatory environments in RA joint.Inspired by neutrophil chemotaxis for inflammatory region,we therefore developed neutrophil-derived exosomes functionalized with sub-5 nm ultrasmall Prussian blue nanoparticles(uPB-Exo)via click chemistry,inheriting neutrophil-targeted biological molecules and owning excellent anti-inflammatory properties.uPB-Exo can selectively accumulate in activated fibroblast-like synoviocytes,subsequently neutralizing pro-inflammatory factors,scavenging reactive oxygen species,and alleviating inflammatory stress.In addition,uPB-Exo effectively targeted to inflammatory synovitis,penetrated deeply into the cartilage and real-time visualized inflamed joint through MRI system,leading to precise diagnosis of RA in vivo with high sensitivity and specificity.Particularly,uPB-Exo induced a cascade of anti-inflammatory events via Th17/Treg cell balance regulation,thereby significantly ameliorating joint damage.Therefore,nanoenzyme functionalized exosomes hold the great potential for enhanced treatment of RA in clinic.
基金the National Natural Science Foundation of China(Nos:22075289,21875254,31771095,and 52073287).
文摘Neuroinflammation is one of the three important pathological features in neurodegenerative diseases including Parkinson’s disease(PD).The regulation of neuroinflammation can reduce the severity of neurological damage to alleviate diseases.Numerous studies have shown that the phenotype switch of microglia is tightly associated with the nuclear factorκB(NF-κB)-mediated inflammatory pathway.Therefore,the small interfering RNA(siRNA)therapy for downregulating the expression of NF-κB,provides a promising therapeutic strategy for Parkinson’s disease treatments.Considering the brain delivery challenges of siRNA,a sequential targeting inflammation regulation(STIR)delivery system based on poly(amino acid)s is developed to improve the therapeutic effects of Parkinson’s disease treatments.The STIR system sequentially targets the blood–brain barrier and the microglia to enhance the effective concentration of siRNA in the targeted microglia.The results demonstrate that the STIR nanoparticles can transform microglial phenotypes and regulate brain inflammation,thus achieving neuronal recovery and abnormal aggregation ofα-synuclein protein(α-syn)reduction in the treatment of Parkinson’s disease.Herein,this STIR delivery system provides a promising therapeutic platform in PD treatments and has great potential for other neurodegenerative diseases’therapies.
