Despite advances in diagnostic and therapeutic technologies for cardiovascular diseases(CVDs),it remains a leading cause of mortality and morbidity worldwide.This underscores the urgency for innovative approaches aimi...Despite advances in diagnostic and therapeutic technologies for cardiovascular diseases(CVDs),it remains a leading cause of mortality and morbidity worldwide.This underscores the urgency for innovative approaches aiming at early and precise detection and treatment of CVDs to reduce the disease burden.Iron oxide nanoparticles(IONPs),with their unique magnetism and bioproperties,have shown great potential in this regard.In this review,we will begin with a brief overview of the synthesis and properties of IONPs.We will then focus on the latest applications of IONPs in CVDs,including diagnosis and treatment.The use of IONPs in the integration of diagnosis and treatment for CVDs is a promising field,and will be addressed in a separate section.The translational potential and challenges of IONPs will also be discussed.In conclusion,ongoing research and development of IONP-based strategies are highly likely to address current challenges effectively,and offer more personalized and efficient options for the diagnosis and treatment of CVDs.展开更多
Iron oxide nanoparticles(IONPs)modified with functional proteins hold great promise in the biomedical field.However,conventional protein modification strategies,such as adsorption and covalent coupling,are either unst...Iron oxide nanoparticles(IONPs)modified with functional proteins hold great promise in the biomedical field.However,conventional protein modification strategies,such as adsorption and covalent coupling,are either unstable or nonspecific,or may result in the changes of protein structure and ultimately the loss of protein activity.Modification of active proteins on small-sized IONPs with a particle size of less than 30 nm is especially difficult due to their high surface energy.Herein,we developed a universal modifica-tion method based on Spy chemistry for rapid and stable protein immobilization on small-sized IONPs,which only requires the presence of active groups on the surface of nanoparticles that can couple with SpyCatcher.In short,the SpyCatcher peptides were first coated on the surface of IONPs by cross-linking with activated groups,and then the SpyTag peptide fused with a model protein(enhanced green fluo-rescent protein,EGFP)was engineered(SpyTag-EGFP)and directly coupled to SpyCatcher-modified IONPs by self-assembly,which is spontaneous and robust while avoiding the effect of chemical reactions on functional protein activity.The obtained EGFP-functionalized IONPs exhibited enhanced and stable green fluorescence and improved magnetic properties.In addition,the cell internalization efficiency of EGFP-functionalized IONPs was significantly increased as compared to unmodified IONPs,providing an ideal solution for efficient cell labeling and tracking.In conclusion,here we report a rapid and easy strategy for EGFP immobilization on IONPs based on Spy chemistry,which could be further adapted to other functional proteins in the future.SpyCatcher-modified IONPs and SpyTag-X(arbitrary functional fusion proteins)hold great potential to be applied as a versatile platform for protein immobilization on IONPs and enable its multifunctional application in the future.展开更多
Labeling of mesenchymal stem cells(MSCs)with superparamagnetic iron oxide nanoparticles(SPIONs)has emerged as a potential method for magnetic resonance imaging(MRI)tracking of transplanted cells in tissue repair studi...Labeling of mesenchymal stem cells(MSCs)with superparamagnetic iron oxide nanoparticles(SPIONs)has emerged as a potential method for magnetic resonance imaging(MRI)tracking of transplanted cells in tissue repair studies and clinical trials.Labeling of MSCs using clinically approved SPIONs(ferumoxytol)requires the use of transfection reagents or magnetic field,which largely limits their clinical application.To overcome this obstacle,we established a novel and highly effective method for magnetic labeling of MSC spheroids using ferumoxytol.Unlike conventional methods,ferumoxytol labeling was done in the formation of a mechanically tunable biomimetic hydrogel-induced MSC spheroids.Moreover,the labeled MSC spheroids exhibited strong MRI T2 signals and good biosafety.Strikingly,the encapsulated ferumoxytol was localized in the extracellular matrix(ECM)of the spheroids instead of the cytoplasm,minimizing the cytotoxicity of ferumoxytol and maintaining the viability and stemness properties of biomimetic hydrogel-induced MSC spheroids.This demonstrates the potential of this method for post-transplantation MRI tracking in the clinic.展开更多
文摘Despite advances in diagnostic and therapeutic technologies for cardiovascular diseases(CVDs),it remains a leading cause of mortality and morbidity worldwide.This underscores the urgency for innovative approaches aiming at early and precise detection and treatment of CVDs to reduce the disease burden.Iron oxide nanoparticles(IONPs),with their unique magnetism and bioproperties,have shown great potential in this regard.In this review,we will begin with a brief overview of the synthesis and properties of IONPs.We will then focus on the latest applications of IONPs in CVDs,including diagnosis and treatment.The use of IONPs in the integration of diagnosis and treatment for CVDs is a promising field,and will be addressed in a separate section.The translational potential and challenges of IONPs will also be discussed.In conclusion,ongoing research and development of IONP-based strategies are highly likely to address current challenges effectively,and offer more personalized and efficient options for the diagnosis and treatment of CVDs.
基金This work was financially supported by the National Natural Science Innovative Research Group Project(No.61821002)the Key Project of the National Natural Science Foundation of China(No.92163213)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK20220824)the Nanjing Science and Technology Develop-ment Foundation(No.202205066).
文摘Iron oxide nanoparticles(IONPs)modified with functional proteins hold great promise in the biomedical field.However,conventional protein modification strategies,such as adsorption and covalent coupling,are either unstable or nonspecific,or may result in the changes of protein structure and ultimately the loss of protein activity.Modification of active proteins on small-sized IONPs with a particle size of less than 30 nm is especially difficult due to their high surface energy.Herein,we developed a universal modifica-tion method based on Spy chemistry for rapid and stable protein immobilization on small-sized IONPs,which only requires the presence of active groups on the surface of nanoparticles that can couple with SpyCatcher.In short,the SpyCatcher peptides were first coated on the surface of IONPs by cross-linking with activated groups,and then the SpyTag peptide fused with a model protein(enhanced green fluo-rescent protein,EGFP)was engineered(SpyTag-EGFP)and directly coupled to SpyCatcher-modified IONPs by self-assembly,which is spontaneous and robust while avoiding the effect of chemical reactions on functional protein activity.The obtained EGFP-functionalized IONPs exhibited enhanced and stable green fluorescence and improved magnetic properties.In addition,the cell internalization efficiency of EGFP-functionalized IONPs was significantly increased as compared to unmodified IONPs,providing an ideal solution for efficient cell labeling and tracking.In conclusion,here we report a rapid and easy strategy for EGFP immobilization on IONPs based on Spy chemistry,which could be further adapted to other functional proteins in the future.SpyCatcher-modified IONPs and SpyTag-X(arbitrary functional fusion proteins)hold great potential to be applied as a versatile platform for protein immobilization on IONPs and enable its multifunctional application in the future.
基金supported by the National Key Research and Development Program of China(2017YFA0104302)the National Natural Science Foundation of China(51832001,61821002,81870807),the China Postdoctoral Science Foundation(2017M621787)the Talent Introduction Foundation of Nanjing Medical University(2017RC07).
文摘Labeling of mesenchymal stem cells(MSCs)with superparamagnetic iron oxide nanoparticles(SPIONs)has emerged as a potential method for magnetic resonance imaging(MRI)tracking of transplanted cells in tissue repair studies and clinical trials.Labeling of MSCs using clinically approved SPIONs(ferumoxytol)requires the use of transfection reagents or magnetic field,which largely limits their clinical application.To overcome this obstacle,we established a novel and highly effective method for magnetic labeling of MSC spheroids using ferumoxytol.Unlike conventional methods,ferumoxytol labeling was done in the formation of a mechanically tunable biomimetic hydrogel-induced MSC spheroids.Moreover,the labeled MSC spheroids exhibited strong MRI T2 signals and good biosafety.Strikingly,the encapsulated ferumoxytol was localized in the extracellular matrix(ECM)of the spheroids instead of the cytoplasm,minimizing the cytotoxicity of ferumoxytol and maintaining the viability and stemness properties of biomimetic hydrogel-induced MSC spheroids.This demonstrates the potential of this method for post-transplantation MRI tracking in the clinic.