Superparamagnetic iron oxide nanoparticles(SPIONs)have immeasurable potentials in many fields such as nanobiotechnology and biomedical engineering because of their superparamagnetic properties and small particle size....Superparamagnetic iron oxide nanoparticles(SPIONs)have immeasurable potentials in many fields such as nanobiotechnology and biomedical engineering because of their superparamagnetic properties and small particle size.This review introduces the methods for SPIONs synthesis,including co-precipitation,thermal decomposition,microemulsion and hydrothermal reaction,and surface modification of SPIONs with organometallic and inorganic metals,surface modification for targeted drug delivery,and the use of SPIONs as a contrast agent.In addition,this article also provides an overview of recent progress in SPIONs for the treatment of glioma,lung cancer and breast cancer.展开更多
Biodistribution and toxicity assessment are critical for safe clinical use of newly developed medicines.Superparamagnetic iron oxide nanoparticles (SPION)are effective carriers for targeted drug delivery.This study ai...Biodistribution and toxicity assessment are critical for safe clinical use of newly developed medicines.Superparamagnetic iron oxide nanoparticles (SPION)are effective carriers for targeted drug delivery.This study aimed to examine the toxicity and biodistribution of SPION coated with polyethylenimine (PEI)(SPION-PEI)designed for small interfering RNA (siRNA) delivery both in vitro and in vivo.SPION-PEI/siRNA complexes were prepared at different weight ratios.Cytotoxic effects of SPION-PEI/siRNA on HSC-T6 cell viability were determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT).Rats were divided into three groups:a control group,a normal-saline group and a SPION-PEI/siRNA group.After a single intravenous injection,in vivo nanoparticle biodistribution and accumulation were evaluated by Prussian blue staining in the heart,liver,spleen,lung and kidney 8 h,24 h,and 7 days after the injection.Their distribution was histologically studied at the three time points by measuring ironpositive areas (μm2)in organ sections stained with Prussian blue.The same organs were analyzed by H&E staining for any possible histopathological changes.Furthermore,biochemical indexes such as alanine amino transaminase (ALT),aspartate transaminase (AST),blood urea nitrogen (BUN)and creatinine (CREA)were also assessed at all experimental time points.Electrophoresis exhibited that the SPION-PEI could retard siRNA altogether at weight ratios above 4.MTT assay showed that SPION-PEI loaded with siRNA had low cytotoxicity.In vivo study revealed that the liver and spleen were the major sites of SPION-PEI/siRNA deposition.The iron content was significantly increased in the liver and spleen,peaking 24 h after intravenous injection and then declining gradually.No evidence was found of irreversible histopathological damage to any of the organs tested.These results suggested that most SPION-PEI/siRNA complexes were distributed in the liver and spleen,which might be the target organs of SPION-PEI/siRNA complexes.SPION- PEI/siRNA may serve as in vivo carrier for biomedical medicines.展开更多
Superparamagnetic iron oxide nanoparticles(SPIONs) are one of the most versatile and safe nanoparticles in a wide variety of biomedical applications. In the past decades, considerable efforts have been made to investi...Superparamagnetic iron oxide nanoparticles(SPIONs) are one of the most versatile and safe nanoparticles in a wide variety of biomedical applications. In the past decades, considerable efforts have been made to investigate the potential adverse biological effects and safety issues associated with SPIONs, which is essential for the development of next-generation SPIONs and for continued progress in translational research. In this mini review, we summarize recent developments in toxicity studies on SPIONs, focusing on the relationship between the physicochemical properties of SPIONs and their induced toxic biological responses for a better toxicological understanding of SPIONs.展开更多
Due to their very small size,nanoparticles can interact with all cells in the central nervous system.One of the most promising nanoparticle subgroups are very small superparamagnetic iron oxide nanoparticles(VSOP)that...Due to their very small size,nanoparticles can interact with all cells in the central nervous system.One of the most promising nanoparticle subgroups are very small superparamagnetic iron oxide nanoparticles(VSOP)that are citrate coated for electrostatic stabilization.To determine their influence on murine blood-derived monocytes,which easily enter the injured central nervous system,we applied VSOP and carboxydextran-coated superparamagnetic iron oxide nanoparticles(Resovist).We assessed their impact on the viability,cytokine,and chemokine secretion,as well as iron uptake of murine blood-derived monocytes.We found that(1)the monocytes accumulated VSOP and Resovist,(2)this uptake seemed to be nanoparticle-and time-dependent,(3)the decrease of monocytes viability was treatment-related,(4)VSOP and Resovist incubation did not alter cytokine homeostasis,and(5)overall a 6-hour treatment with 0.75 mM VSOP-R1 was probably sufficient to effectively label monocytes for future experiments.Since homeostasis is not altered,it is safe to label blood-derived monocles with VSOP.VSOP labeled monocytes can be used to study injured central nervous system sites further,for example with drug-carrying VSOP.展开更多
Recent progress of the preparation and applications of superparamagnetic iron oxide(SPIO) clusters as magnetic resonance imaging(MRI) probes is reviewed with regard to their applications in labeling and tracking cells...Recent progress of the preparation and applications of superparamagnetic iron oxide(SPIO) clusters as magnetic resonance imaging(MRI) probes is reviewed with regard to their applications in labeling and tracking cells in vivo, in diagnosis of cardiovascular diseases and tumors, and in drug delivery systems. Magnetic nanoparticles(NPs), especially SPIO nanoparticles, have long been used as MRI contrast agents and as an advantageous nanoplatform for drug delivery,taking advantage of their unique magnetic properties and ability to function at the molecular and cellular levels. Due to advances in nanotechnology, various means to control SPIO NPs' size, composition, magnetization and relaxivity have been developed, as well as ways to usefully modify their surface. Recently, self-assembly of SPIO NP clusters in particulate carriers — such as polymeric micelles, vesicles, liposomes, and layer-by-layer(Lb L) capsules — have been widely studied for application as ultrasensitive MRI probes, owing to their remarkably high spin–spin(T2) relaxivity and convenience for further functionalization.展开更多
Age-related macular degeneration(AMD) is the leading cause of vision loss in the elderly throughout the world. Treatment of AMD utilizing retinal pigment epithelium(RPE) transplantation represents a promising therapy....Age-related macular degeneration(AMD) is the leading cause of vision loss in the elderly throughout the world. Treatment of AMD utilizing retinal pigment epithelium(RPE) transplantation represents a promising therapy. However, simplex RPE transplantation can only replace the diseased RPE cells, but has no abilities to stop the development of AMD. It has been indicated that oxidization triggers the development of AMD by inducing the dysfunction and degeneration of RPE cells, which results in the upregulation of local monocyte chemotactic protein-1(MCP-1) expression. MCP-1 induces macrophage recruiment which triggers local inflammation. As a result, the expression of vascular endothelial growth factor(VEGF) is upregulated by MCP-1mediated inflammation and results in the formation of choroidal neovascularization(CNV). We accordingly propose a targeted therapy of AMD by subretinal transplanting the compound of RPE cell, MCP-1 antibody, and VEGF antibody and using a magnetic system to guide RPE cell compounds conjugated with superparamagnetic iron oxide nanoparticles(SPIONs). Furthermore, SPION-labelled RPE cells can be tracked and detected in vivo by non-invasive magnetic resonance imaging(MRI). This novel RPE cell transplantation methodology seems very promising to provide a new therapeutic approach for the treatment of AMD.展开更多
Superparamagnetic iron oxide(SPIO)nanoparticles have become a popular strategy of cancer treatment and molecular imaging because of their versatile properties and biocompatibility.A variety of studies have shown the e...Superparamagnetic iron oxide(SPIO)nanoparticles have become a popular strategy of cancer treatment and molecular imaging because of their versatile properties and biocompatibility.A variety of studies have shown the exciting potential of functionalized SPIO nanoparticles,such as surface-coated,targeted ligandconjugated,and/or drug-loaded SPIO nanoparticles,as powerful tools for targeted imaging and therapy.Moreover,the applications of SPIO nanoparticles that integrate diagnosis and therapy in SPIO nanoparticles facilitate the monitoring of therapeutic efficacy during treatment.In the present review,we primarily concentrate on the recent advancements in the field of SPIO nanoparticles in terms of synthesis,targeted therapy,and cancer imaging.展开更多
Background:In vivo cell tracking after transplantation in regenerative medicine remains an unmet challenge and limits current understanding of the wound healing mechanism through cell-based therapies.This study invest...Background:In vivo cell tracking after transplantation in regenerative medicine remains an unmet challenge and limits current understanding of the wound healing mechanism through cell-based therapies.This study investigated tracking of human Wharton’s jelly stem cells(hWJSCs)seeded onto an acellular dermal matrix(ADM)and labeled with superparamagnetic iron oxide nanoparti-cles(SPIONs)by magnetic resonance imaging(MRI)in burn injury.Method:The hWJSCs were characterized and assessed for growth kinetics.A total of 30 rats were enrolled in three equal groups.Group 1 underwent scald burn injury left without treatment,the group 2 was treated by an ADM that was prepared from cosmetic surgery skin samples and the group 3 received hWJSCs labeled with SPIONs seeded onto an ADM.Tensile strength was evaluated before and after interventions,real time PCR assessed apoptosis,and Prussian blue staining,scanning electron microscopy(SEM)and MRI were used for the tracking of labeled cells.Results:The hWJSCs exhibited mesenchymal stem cell properties.Population doubling time was 40.1 hours.SPIONs did not show any toxic effect.The hWJSCs seeded onto an ADM decreased Bax and increased Bcl-2 gene expression.Internalization of SPIONs within hWJSCs was confirmed by Prussian blue staining,SEM and MRI until day 21.There was a significant difference between the Young’s moduli of normal skin and the group receiving hWJSCs seeded onto an ADM.Histological observations and SEM imaging confirmed that MRI is an accurate method to track SPION-labeled hWJSCs in vivo.Conclusions:This study showed that SPION labeling coupled with MRI can be used to further understand the fate of stem cells after transplantation in a burn model.展开更多
超顺磁性氧化铁纳米粒子(superparamagnetic iron oxide nanoparticle, SPION)由于其独特的性质,如低毒、生物相容性、强大的磁性,以及在多功能模式中的优越作用,在肿瘤诊断、构建多模态肿瘤分子影像探针及治疗方面展现出巨大的潜力,今...超顺磁性氧化铁纳米粒子(superparamagnetic iron oxide nanoparticle, SPION)由于其独特的性质,如低毒、生物相容性、强大的磁性,以及在多功能模式中的优越作用,在肿瘤诊断、构建多模态肿瘤分子影像探针及治疗方面展现出巨大的潜力,今后可以在临床上提高肿瘤诊断的特异性、敏感性,实现诊疗一体化,本文从SPION的成像机制、合成方法出发,阐述近年来SPION在肿瘤的各种靶向成像、多模态成像和治疗方面的研究进展,展望未来SPION在肿瘤诊断及治疗中的发展前景,旨在为更好地构建基于SPION的新型诊疗一体化肿瘤探针提供参考。展开更多
基金Supported by National Natural Science Foundation of China(32060228)。
文摘Superparamagnetic iron oxide nanoparticles(SPIONs)have immeasurable potentials in many fields such as nanobiotechnology and biomedical engineering because of their superparamagnetic properties and small particle size.This review introduces the methods for SPIONs synthesis,including co-precipitation,thermal decomposition,microemulsion and hydrothermal reaction,and surface modification of SPIONs with organometallic and inorganic metals,surface modification for targeted drug delivery,and the use of SPIONs as a contrast agent.In addition,this article also provides an overview of recent progress in SPIONs for the treatment of glioma,lung cancer and breast cancer.
基金the National Natural Science Foundation of China(Nos.81402640,81502816)the Natural Science Foundation of Hubei Province(No.2014CFB406)+1 种基金the Health and Family Planning Commission of Wuhan City(No.WX15B23)Training Plan for Young and Middleaged Backbone Talents in Wuhan[No.2014(77)].
文摘Biodistribution and toxicity assessment are critical for safe clinical use of newly developed medicines.Superparamagnetic iron oxide nanoparticles (SPION)are effective carriers for targeted drug delivery.This study aimed to examine the toxicity and biodistribution of SPION coated with polyethylenimine (PEI)(SPION-PEI)designed for small interfering RNA (siRNA) delivery both in vitro and in vivo.SPION-PEI/siRNA complexes were prepared at different weight ratios.Cytotoxic effects of SPION-PEI/siRNA on HSC-T6 cell viability were determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT).Rats were divided into three groups:a control group,a normal-saline group and a SPION-PEI/siRNA group.After a single intravenous injection,in vivo nanoparticle biodistribution and accumulation were evaluated by Prussian blue staining in the heart,liver,spleen,lung and kidney 8 h,24 h,and 7 days after the injection.Their distribution was histologically studied at the three time points by measuring ironpositive areas (μm2)in organ sections stained with Prussian blue.The same organs were analyzed by H&E staining for any possible histopathological changes.Furthermore,biochemical indexes such as alanine amino transaminase (ALT),aspartate transaminase (AST),blood urea nitrogen (BUN)and creatinine (CREA)were also assessed at all experimental time points.Electrophoresis exhibited that the SPION-PEI could retard siRNA altogether at weight ratios above 4.MTT assay showed that SPION-PEI loaded with siRNA had low cytotoxicity.In vivo study revealed that the liver and spleen were the major sites of SPION-PEI/siRNA deposition.The iron content was significantly increased in the liver and spleen,peaking 24 h after intravenous injection and then declining gradually.No evidence was found of irreversible histopathological damage to any of the organs tested.These results suggested that most SPION-PEI/siRNA complexes were distributed in the liver and spleen,which might be the target organs of SPION-PEI/siRNA complexes.SPION- PEI/siRNA may serve as in vivo carrier for biomedical medicines.
基金Project supported by the Major State Basic Research Development Program of China(Grant Nos.2013CB733802 and 2014CB744503)the National Natural Science Foundation of China(Grant Nos.81101101 and 51273165)+1 种基金the Key Project of Chinese Ministry of Education(Grant No.212149)the Fundamental Research Funds for the Central Universities,China(Grant Nos.2013121039 and ZK1002)
文摘Superparamagnetic iron oxide nanoparticles(SPIONs) are one of the most versatile and safe nanoparticles in a wide variety of biomedical applications. In the past decades, considerable efforts have been made to investigate the potential adverse biological effects and safety issues associated with SPIONs, which is essential for the development of next-generation SPIONs and for continued progress in translational research. In this mini review, we summarize recent developments in toxicity studies on SPIONs, focusing on the relationship between the physicochemical properties of SPIONs and their induced toxic biological responses for a better toxicological understanding of SPIONs.
基金supported by Deutsche Forschungsgemeinschaft(DFG)grant Klinische Forschergruppe(KFO)213(to JG).
文摘Due to their very small size,nanoparticles can interact with all cells in the central nervous system.One of the most promising nanoparticle subgroups are very small superparamagnetic iron oxide nanoparticles(VSOP)that are citrate coated for electrostatic stabilization.To determine their influence on murine blood-derived monocytes,which easily enter the injured central nervous system,we applied VSOP and carboxydextran-coated superparamagnetic iron oxide nanoparticles(Resovist).We assessed their impact on the viability,cytokine,and chemokine secretion,as well as iron uptake of murine blood-derived monocytes.We found that(1)the monocytes accumulated VSOP and Resovist,(2)this uptake seemed to be nanoparticle-and time-dependent,(3)the decrease of monocytes viability was treatment-related,(4)VSOP and Resovist incubation did not alter cytokine homeostasis,and(5)overall a 6-hour treatment with 0.75 mM VSOP-R1 was probably sufficient to effectively label monocytes for future experiments.Since homeostasis is not altered,it is safe to label blood-derived monocles with VSOP.VSOP labeled monocytes can be used to study injured central nervous system sites further,for example with drug-carrying VSOP.
基金Project supported by the National Key Basic Research Program of China(Grant No.2013CB933903)the National Natural Science Foundation of China(Grant Nos.20974065+2 种基金51173117and 50830107)the Scientific Research Start-up Fund of Kunming University of Science and Technology(Grant No.KKSY201305089)
文摘Recent progress of the preparation and applications of superparamagnetic iron oxide(SPIO) clusters as magnetic resonance imaging(MRI) probes is reviewed with regard to their applications in labeling and tracking cells in vivo, in diagnosis of cardiovascular diseases and tumors, and in drug delivery systems. Magnetic nanoparticles(NPs), especially SPIO nanoparticles, have long been used as MRI contrast agents and as an advantageous nanoplatform for drug delivery,taking advantage of their unique magnetic properties and ability to function at the molecular and cellular levels. Due to advances in nanotechnology, various means to control SPIO NPs' size, composition, magnetization and relaxivity have been developed, as well as ways to usefully modify their surface. Recently, self-assembly of SPIO NP clusters in particulate carriers — such as polymeric micelles, vesicles, liposomes, and layer-by-layer(Lb L) capsules — have been widely studied for application as ultrasensitive MRI probes, owing to their remarkably high spin–spin(T2) relaxivity and convenience for further functionalization.
基金Supported by the National Natural Science Foundation of China(No.81100670)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry of China
文摘Age-related macular degeneration(AMD) is the leading cause of vision loss in the elderly throughout the world. Treatment of AMD utilizing retinal pigment epithelium(RPE) transplantation represents a promising therapy. However, simplex RPE transplantation can only replace the diseased RPE cells, but has no abilities to stop the development of AMD. It has been indicated that oxidization triggers the development of AMD by inducing the dysfunction and degeneration of RPE cells, which results in the upregulation of local monocyte chemotactic protein-1(MCP-1) expression. MCP-1 induces macrophage recruiment which triggers local inflammation. As a result, the expression of vascular endothelial growth factor(VEGF) is upregulated by MCP-1mediated inflammation and results in the formation of choroidal neovascularization(CNV). We accordingly propose a targeted therapy of AMD by subretinal transplanting the compound of RPE cell, MCP-1 antibody, and VEGF antibody and using a magnetic system to guide RPE cell compounds conjugated with superparamagnetic iron oxide nanoparticles(SPIONs). Furthermore, SPION-labelled RPE cells can be tracked and detected in vivo by non-invasive magnetic resonance imaging(MRI). This novel RPE cell transplantation methodology seems very promising to provide a new therapeutic approach for the treatment of AMD.
基金This work was supported by the Natural Science Foundation of Hubei Province(Grant No.2009HBKJH1).
文摘Superparamagnetic iron oxide(SPIO)nanoparticles have become a popular strategy of cancer treatment and molecular imaging because of their versatile properties and biocompatibility.A variety of studies have shown the exciting potential of functionalized SPIO nanoparticles,such as surface-coated,targeted ligandconjugated,and/or drug-loaded SPIO nanoparticles,as powerful tools for targeted imaging and therapy.Moreover,the applications of SPIO nanoparticles that integrate diagnosis and therapy in SPIO nanoparticles facilitate the monitoring of therapeutic efficacy during treatment.In the present review,we primarily concentrate on the recent advancements in the field of SPIO nanoparticles in terms of synthesis,targeted therapy,and cancer imaging.
文摘Background:In vivo cell tracking after transplantation in regenerative medicine remains an unmet challenge and limits current understanding of the wound healing mechanism through cell-based therapies.This study investigated tracking of human Wharton’s jelly stem cells(hWJSCs)seeded onto an acellular dermal matrix(ADM)and labeled with superparamagnetic iron oxide nanoparti-cles(SPIONs)by magnetic resonance imaging(MRI)in burn injury.Method:The hWJSCs were characterized and assessed for growth kinetics.A total of 30 rats were enrolled in three equal groups.Group 1 underwent scald burn injury left without treatment,the group 2 was treated by an ADM that was prepared from cosmetic surgery skin samples and the group 3 received hWJSCs labeled with SPIONs seeded onto an ADM.Tensile strength was evaluated before and after interventions,real time PCR assessed apoptosis,and Prussian blue staining,scanning electron microscopy(SEM)and MRI were used for the tracking of labeled cells.Results:The hWJSCs exhibited mesenchymal stem cell properties.Population doubling time was 40.1 hours.SPIONs did not show any toxic effect.The hWJSCs seeded onto an ADM decreased Bax and increased Bcl-2 gene expression.Internalization of SPIONs within hWJSCs was confirmed by Prussian blue staining,SEM and MRI until day 21.There was a significant difference between the Young’s moduli of normal skin and the group receiving hWJSCs seeded onto an ADM.Histological observations and SEM imaging confirmed that MRI is an accurate method to track SPION-labeled hWJSCs in vivo.Conclusions:This study showed that SPION labeling coupled with MRI can be used to further understand the fate of stem cells after transplantation in a burn model.
文摘超顺磁性氧化铁纳米粒子(superparamagnetic iron oxide nanoparticle, SPION)由于其独特的性质,如低毒、生物相容性、强大的磁性,以及在多功能模式中的优越作用,在肿瘤诊断、构建多模态肿瘤分子影像探针及治疗方面展现出巨大的潜力,今后可以在临床上提高肿瘤诊断的特异性、敏感性,实现诊疗一体化,本文从SPION的成像机制、合成方法出发,阐述近年来SPION在肿瘤的各种靶向成像、多模态成像和治疗方面的研究进展,展望未来SPION在肿瘤诊断及治疗中的发展前景,旨在为更好地构建基于SPION的新型诊疗一体化肿瘤探针提供参考。