Osteoporosis presents a marked global public health challenge,characterized by deficient osteogenesis and a deteriorating immune microenvironment.Conventional clinical interventions primarily target osteoclast-mediate...Osteoporosis presents a marked global public health challenge,characterized by deficient osteogenesis and a deteriorating immune microenvironment.Conventional clinical interventions primarily target osteoclast-mediated bone damage,yet lack a comprehensive therapeutic approach that balances bone formation and resorption.Herein,we introduce a bone-targeted nanocomposite,A-Z@Pd(H),designed to address these challenges by integrating diverse functional components.The nanocomposite incorporates internal hydrogen-carrying nanozymes,which effectively scavenge multiple reactive oxygen species(ROS)and synergistically engage the autophagy–lysosome pathway to accelerate endogenous ROS degradation in macrophages.This mechanism disrupts the vicious cycle of autophagic dysfunction–ROS accumulation–macrophage inflammation.In addition,external metal–organic frameworks release zinc ions(Zn^(2+))in response to the acidic osteoporotic environment,thereby promoting osteogenesis.In a murine model of osteoporosis,intravenous administration of A-Z@Pd(H)leads to preferential accumulation in the femur,thereby remodeling the osteoporotic microenvironment through immune regulation,osteogenesis promotion,and osteoclast inhibition.These findings suggest that this system composed of hydrogen therapy and ion therapy may be a promising candidate for bone-targeted comprehensive therapy in osteoporosis.展开更多
The tumormicroenvironment is a complex and heterogeneous milieu characterized by the interaction between diverse cellular and non-cellular constituents.This intricate ecosystem,intrinsic to gastrointestinal(GI)cancers...The tumormicroenvironment is a complex and heterogeneous milieu characterized by the interaction between diverse cellular and non-cellular constituents.This intricate ecosystem,intrinsic to gastrointestinal(GI)cancers,encompasses elements such as the local microbiome,specific species like Helicobacter pylori,distinct immune cell subsets,and stromal cell components.The interplay between these components intricately contributes to the modulation of tumor progressiondynamicsand shapes the responses ofGI neoplasms to therapeutic interventions.A comprehensive understanding of these nuanced interactions is pivotal to elucidate the underlying complexities of GI cancers,thereby providing avenues for the strategicmanipulation of these networks,leading tomore efficacious therapeutic strategies.展开更多
A tumor cell membrane(CM)-based biomimetic membrane tumor vaccine is an emerging prevention and treatment strategy in tumor immunotherapy.However,a single CM mostly has a weak immune-boosting effect.Here,a heterogenic...A tumor cell membrane(CM)-based biomimetic membrane tumor vaccine is an emerging prevention and treatment strategy in tumor immunotherapy.However,a single CM mostly has a weak immune-boosting effect.Here,a heterogenic fusion membrane tumor vaccine,EV–CM,was successfully constructed by fusing extracellular vesicles(EVs)from S.aureus and CM from B16F10 melanoma cells.Inheriting the advantages of parental components,the EV–CM combines tumor antigens with natural adjuvants that can be used for immunotherapy and can be easily synergistic with complementary therapies.In vivo vaccine tests have shown that EV–CM can activate immune antitumor responses and prevent tumorigenesis.To further enhance the immunotherapeutic and antimetastatic effects of EV–CM,Pt-porphyrin coordination polymer as an immunopotentiator(CPIP)was implanted into an EV–CM nanoplatform(CPIP@EV–CM),which combines localized sonodynamic/chemodynamic therapy-induced immunogenic cell death with heterogenic fusion membrane-mediated antigen-presenting functions.In vitro performance tests,cell experiments,and in vivo animal models have confirmed that the CPIP@EV–CM combined with US has better ROS production,tumor cell killing,and antimetastasis abilities.The heterogenic fusion membrane strategy and ultrasound-augmented nanoplatform present exciting prospects for designing tumor-immunogenic,self-adjuvant,and expandable vaccines,providing new ideas for exploring new melanoma immunotherapy and antimetastasis strategies,which is expected to be used as a safe and effective treatment in clinical practice.展开更多
CONSPECTUS:The microfluidic biochemical/immunoassay systems typically consist of microfluidic chips,fluid driving devices,and detection components.The core of the system is the microfluidic chips based on microfluidic...CONSPECTUS:The microfluidic biochemical/immunoassay systems typically consist of microfluidic chips,fluid driving devices,and detection components.The core of the system is the microfluidic chips based on microfluidic technology,which are typically constructed with nonresponsive materials such as silicon,glass,and rigid plastics,thus requiring complex external air/liquid pumps to manipulate the samples.The external equipment renders the microfluidic systems cumbersome and increases the risk of biosample contamination.展开更多
基金funded by the Jiangxi Province Key Laboratory of Precision Cell Therapy(no.2024SSY06241 to J.L.)the National Key Research and Development Program of China(no.2020YFC2005800 to J.L.)+7 种基金the National Natural Science Foundation of China(no.82360174 to J.L.and no.82360424 to J.Y.)the Natural Science Foundation of Jiangxi Province(20113BCB22005 and 20181BCG42001 to J.L.)the Science and Technology Department Project of Jiangxi Province(20224ABC03A02 to J.L.)the Second Affiliated Hospital of Nanchang University-funded projects(grant no.2022efyB03 to J.L.)the Key Research and Development Program of Jiangxi Province(20212BBG73004 to X.W.)the Interdiscipline Innovation Fund Project of Nanchang University(PYJX20230001 to X.W.)the Graduate Innovation Special Fund Project of Jiangxi Province(YC2023-B046 to L.L.)the Science and Technology Program of Jiangxi Provincial Health Commission(202410028 to H.L.).
文摘Osteoporosis presents a marked global public health challenge,characterized by deficient osteogenesis and a deteriorating immune microenvironment.Conventional clinical interventions primarily target osteoclast-mediated bone damage,yet lack a comprehensive therapeutic approach that balances bone formation and resorption.Herein,we introduce a bone-targeted nanocomposite,A-Z@Pd(H),designed to address these challenges by integrating diverse functional components.The nanocomposite incorporates internal hydrogen-carrying nanozymes,which effectively scavenge multiple reactive oxygen species(ROS)and synergistically engage the autophagy–lysosome pathway to accelerate endogenous ROS degradation in macrophages.This mechanism disrupts the vicious cycle of autophagic dysfunction–ROS accumulation–macrophage inflammation.In addition,external metal–organic frameworks release zinc ions(Zn^(2+))in response to the acidic osteoporotic environment,thereby promoting osteogenesis.In a murine model of osteoporosis,intravenous administration of A-Z@Pd(H)leads to preferential accumulation in the femur,thereby remodeling the osteoporotic microenvironment through immune regulation,osteogenesis promotion,and osteoclast inhibition.These findings suggest that this system composed of hydrogen therapy and ion therapy may be a promising candidate for bone-targeted comprehensive therapy in osteoporosis.
文摘The tumormicroenvironment is a complex and heterogeneous milieu characterized by the interaction between diverse cellular and non-cellular constituents.This intricate ecosystem,intrinsic to gastrointestinal(GI)cancers,encompasses elements such as the local microbiome,specific species like Helicobacter pylori,distinct immune cell subsets,and stromal cell components.The interplay between these components intricately contributes to the modulation of tumor progressiondynamicsand shapes the responses ofGI neoplasms to therapeutic interventions.A comprehensive understanding of these nuanced interactions is pivotal to elucidate the underlying complexities of GI cancers,thereby providing avenues for the strategicmanipulation of these networks,leading tomore efficacious therapeutic strategies.
基金supported by the National Natural Science Foundation of China(Grant nos.82272003,82302195,and 82371976)the China Postdoctoral Science Foundation(Grant no.2024M752237)+1 种基金the Sichuan Science and Technology Program(Grant no.2024YFHZ0271)PostDoctor Research Project,Sichuan University(Grant nos.2024SCU12029 and 2023SCU12070).
文摘A tumor cell membrane(CM)-based biomimetic membrane tumor vaccine is an emerging prevention and treatment strategy in tumor immunotherapy.However,a single CM mostly has a weak immune-boosting effect.Here,a heterogenic fusion membrane tumor vaccine,EV–CM,was successfully constructed by fusing extracellular vesicles(EVs)from S.aureus and CM from B16F10 melanoma cells.Inheriting the advantages of parental components,the EV–CM combines tumor antigens with natural adjuvants that can be used for immunotherapy and can be easily synergistic with complementary therapies.In vivo vaccine tests have shown that EV–CM can activate immune antitumor responses and prevent tumorigenesis.To further enhance the immunotherapeutic and antimetastatic effects of EV–CM,Pt-porphyrin coordination polymer as an immunopotentiator(CPIP)was implanted into an EV–CM nanoplatform(CPIP@EV–CM),which combines localized sonodynamic/chemodynamic therapy-induced immunogenic cell death with heterogenic fusion membrane-mediated antigen-presenting functions.In vitro performance tests,cell experiments,and in vivo animal models have confirmed that the CPIP@EV–CM combined with US has better ROS production,tumor cell killing,and antimetastasis abilities.The heterogenic fusion membrane strategy and ultrasound-augmented nanoplatform present exciting prospects for designing tumor-immunogenic,self-adjuvant,and expandable vaccines,providing new ideas for exploring new melanoma immunotherapy and antimetastasis strategies,which is expected to be used as a safe and effective treatment in clinical practice.
基金financially supported by the National Natural Science Foundation of China(51927805,52233001)the Innovation Program of Shanghai Municipal Education Commission(2023ZKZD07).
文摘CONSPECTUS:The microfluidic biochemical/immunoassay systems typically consist of microfluidic chips,fluid driving devices,and detection components.The core of the system is the microfluidic chips based on microfluidic technology,which are typically constructed with nonresponsive materials such as silicon,glass,and rigid plastics,thus requiring complex external air/liquid pumps to manipulate the samples.The external equipment renders the microfluidic systems cumbersome and increases the risk of biosample contamination.
