Osteoporosis is a skeletal disorder resulted in significant structural and functional changes,arousing a wide concern for the high prevalence and cost.Imbalance between osteoclastogenesis and osteogenesis have been ve...Osteoporosis is a skeletal disorder resulted in significant structural and functional changes,arousing a wide concern for the high prevalence and cost.Imbalance between osteoclastogenesis and osteogenesis have been verified as a main pathology etiology and considered an efficient therapy target in both clinical and pre-clinical studies.In recent years,inorganic nanomaterials have shown provable activities on osteoclastogenesis inhibition and osteogenesis promotion,respectively.Hence,in this study,a class of hydroxyapatite coated superparamagnetic iron oxide nanoparticles(SPIO@HA)were developed with a coreshell structure for targeting both osteoclastogenesis and osteogenesis.The optimal ratio of SPIO@15HA(Fe/Ca¼1:15,mol/mol)was screened to obtain dual function for inducing both bone formation and preventing bone resorption.The obtained nanocomposites significantly prevented the bone loss of ovariectomized(OVX)mice and increased bone mineral density(BMD)by 9.4%,exhibiting high bone accumulation in magnetic resonance imaging evaluation and reasonable biosafety profile.The mechanism study revealed that SPIO@15HA can suppress bone marrow monocyte derived osteoclast differentiation through TRAF6p62CYLD signaling complex regulation.Meanwhile,it could activate MSC osteogenic differentiation by TGF-b,PI3K-AKT and calcium signaling pathway regulation.Moreover,incubation of SPIO@15HA with MSC resulted in several cytokines overexpression such as osteoprotegerin(OPG),CSF2,CCL2 etc.,which are responsible for maintaining the bone remodeling balance.The dual function of as-prepared SPIO@15HA may find a new way for designing of inorganic components containing core/shell nanomaterials for osteoporosis treatment.展开更多
Magnetic resonance(MR)/optical dual-mode imaging with high sensitivity and high tissue resolution have attracted many attentions in biomedical applications.To avert aggregation-caused quenching of conventional fluores...Magnetic resonance(MR)/optical dual-mode imaging with high sensitivity and high tissue resolution have attracted many attentions in biomedical applications.To avert aggregation-caused quenching of conventional fluorescence chromophores,an aggregation-induced emission molecule tetraphenylethylene(TPE)-conjugated amphiphilic polyethylenimine(PEI)covered superparamagnetic iron oxide(Alkyl-PEI-LAC-TPE/SPIO nanocomposites)was prepared as an MR/optical dual-mode probe.Alkyl-PEI-LAC-TPE/SPIO nanocomposites exhibited good fluorescence property and presented higher T2 relaxivity(352 Fe mM1s1)than a commercial contrast agent Feridex(120 Fe mM1s1)at 1.5 T.The alkylation degree of Alkyl-PEI-LAC-TPE effects the restriction of intramolecular rotation process of TPE.Reducing alkane chain grafting ratio aggravated the stack of TPE,increasing the fluorescence lifetime of Alkyl-PEI-LAC-TPE/SPIO nanocomposites.Alkyl-PEI-LAC-TPE/SPIO nanocomposites can effectively labelled HeLa cells and resulted in high fluorescence intensity and excellent MR imaging sensitivity.As an MR/optical imaging probe,Alkyl-PEI-LAC-TPE/SPIO nanocomposites may be used in biomedical imaging for certain applications.展开更多
Macrophage autophagy is a common biological response triggered by nanomaterials,which is closely related to the regulation of inflammation.Superparamagnetic iron oxide(SPIO)nanoparticles have been used for study of au...Macrophage autophagy is a common biological response triggered by nanomaterials,which is closely related to the regulation of inflammation.Superparamagnetic iron oxide(SPIO)nanoparticles have been used for study of autophagy response due to their broad biomedical applications.However,few reports have focused on how to regulate the macrophage autophagy response induced by SPIO nanoparticles.In this study,SPIO nanoparticles grafted with carboxyl groups were synthesized and for the comparison of macrophage autophagy with unmodified nanoparticles.The study on the correlation between autophagy and inflammation induced by the two kinds of SPIO nanoparticles was also included,and the one that grafted with carboxyl groups shows a reduction of autophagy and thereby caused a milder inflammatory response.We proposed that the increased amount of albumin adsorption on the surface of carboxylated SPIO nanoparticles,a protein previously proven to attenuate autophagy,can be considered an important reason for reducing autophagy and inflammation.In general,the carboxyl modification of SPIO nanoparticles has been demonstrated to reduce inflammation by inhibiting macrophage autophagy,which may provide some insights for the design of nanomaterials in the future.展开更多
The T_(1)-T_(2) dual-mode probes for magnetic resonance imaging(MRI)can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same t...The T_(1)-T_(2) dual-mode probes for magnetic resonance imaging(MRI)can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same time,making MRI a more flexible imaging modality for complicated applications.In this work,three Gadolinium-diethylene-triaminepentaaceticacid(Gd-DTPA)complex conjugated superparamagnetic iron oxide(SPIO)nanoparticles with different Gd/Fe molar ratio(0.94,1.28 and 1.67)were prepared as T_(1)-T_(2) dual-mode MRI probes,named as SPIO@PEG-GdDTPA0.94,SPIO@PEGGdDTPA1.28 and SPIO@PEG-GdDTPA1.67,respectively.All SPIO@PEG-GdDTPA nanocomposites with 8 nm spherical SPIO nanocrystals showed good Gd3þchelate stability.SPIO@PEG-GdDTPA0.94 nanocomposites with lowest Gd/Fe molar ratio show no cytotoxicity to Raw 264.7 cells as compared to SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67.SPIO@PEG-GdDTPA0.94 nanocomposites with r1(8.4mM^(-1)s^(-1)),r2(83.2mM^(-1)s^(-1))and relatively ideal r2/r1 ratio(9.9)were selected for T_(1)-T_(2) dual-mode MRI of blood vessels and liver tissue in vivo.Good contrast images were obtained for both cardiovascular system and liver in animal studies under a clinical 3 T scanner.Importantly,one can get high-quality contrast-enhanced blood vessel images within the first 2 h after contrast agent administration and acquire liver tissue anatomy information up to 24 h.Overall,the strategy of one shot of the dual mode MRI agent could bring numerous benefits not only for patients but also to the radiologists and clinicians,e.g.saving time,lowering side effects and collecting data of different organs sequentially.展开更多
基金supported by National Natural Science Foundation of China(NSFC,Nos 51903174 and 52073192)Innovative Research Groups of the National Natural Science Foundation of China(81621003)+1 种基金Chengdu Science and Technology Program(2019-YF05-00318-SN)the Sichuan University Postdoctoral Interdisciplinary Innovation Startup Foundation and the Fundamental Research Funds for Central Universities(2021SCU12070).
文摘Osteoporosis is a skeletal disorder resulted in significant structural and functional changes,arousing a wide concern for the high prevalence and cost.Imbalance between osteoclastogenesis and osteogenesis have been verified as a main pathology etiology and considered an efficient therapy target in both clinical and pre-clinical studies.In recent years,inorganic nanomaterials have shown provable activities on osteoclastogenesis inhibition and osteogenesis promotion,respectively.Hence,in this study,a class of hydroxyapatite coated superparamagnetic iron oxide nanoparticles(SPIO@HA)were developed with a coreshell structure for targeting both osteoclastogenesis and osteogenesis.The optimal ratio of SPIO@15HA(Fe/Ca¼1:15,mol/mol)was screened to obtain dual function for inducing both bone formation and preventing bone resorption.The obtained nanocomposites significantly prevented the bone loss of ovariectomized(OVX)mice and increased bone mineral density(BMD)by 9.4%,exhibiting high bone accumulation in magnetic resonance imaging evaluation and reasonable biosafety profile.The mechanism study revealed that SPIO@15HA can suppress bone marrow monocyte derived osteoclast differentiation through TRAF6p62CYLD signaling complex regulation.Meanwhile,it could activate MSC osteogenic differentiation by TGF-b,PI3K-AKT and calcium signaling pathway regulation.Moreover,incubation of SPIO@15HA with MSC resulted in several cytokines overexpression such as osteoprotegerin(OPG),CSF2,CCL2 etc.,which are responsible for maintaining the bone remodeling balance.The dual function of as-prepared SPIO@15HA may find a new way for designing of inorganic components containing core/shell nanomaterials for osteoporosis treatment.
基金This work was financially supported by the National Natural Science Foundation of China(NSFC,No.51903174 and 52073192)Innovative Research Groups of the National Natural Science Foundation of China(81621003)+1 种基金Chengdu Science and Technology Program(2019-YF05-00318-SN)the Fundamental Research Funds for Central Universities(2021SCU12070).
文摘Magnetic resonance(MR)/optical dual-mode imaging with high sensitivity and high tissue resolution have attracted many attentions in biomedical applications.To avert aggregation-caused quenching of conventional fluorescence chromophores,an aggregation-induced emission molecule tetraphenylethylene(TPE)-conjugated amphiphilic polyethylenimine(PEI)covered superparamagnetic iron oxide(Alkyl-PEI-LAC-TPE/SPIO nanocomposites)was prepared as an MR/optical dual-mode probe.Alkyl-PEI-LAC-TPE/SPIO nanocomposites exhibited good fluorescence property and presented higher T2 relaxivity(352 Fe mM1s1)than a commercial contrast agent Feridex(120 Fe mM1s1)at 1.5 T.The alkylation degree of Alkyl-PEI-LAC-TPE effects the restriction of intramolecular rotation process of TPE.Reducing alkane chain grafting ratio aggravated the stack of TPE,increasing the fluorescence lifetime of Alkyl-PEI-LAC-TPE/SPIO nanocomposites.Alkyl-PEI-LAC-TPE/SPIO nanocomposites can effectively labelled HeLa cells and resulted in high fluorescence intensity and excellent MR imaging sensitivity.As an MR/optical imaging probe,Alkyl-PEI-LAC-TPE/SPIO nanocomposites may be used in biomedical imaging for certain applications.
基金supported by the National Natural Science Foundation of China(NSFC,No.51903174,52073192)the Innovative Research Groups of the National Natural Science Foundation of China(81621003).
文摘Macrophage autophagy is a common biological response triggered by nanomaterials,which is closely related to the regulation of inflammation.Superparamagnetic iron oxide(SPIO)nanoparticles have been used for study of autophagy response due to their broad biomedical applications.However,few reports have focused on how to regulate the macrophage autophagy response induced by SPIO nanoparticles.In this study,SPIO nanoparticles grafted with carboxyl groups were synthesized and for the comparison of macrophage autophagy with unmodified nanoparticles.The study on the correlation between autophagy and inflammation induced by the two kinds of SPIO nanoparticles was also included,and the one that grafted with carboxyl groups shows a reduction of autophagy and thereby caused a milder inflammatory response.We proposed that the increased amount of albumin adsorption on the surface of carboxylated SPIO nanoparticles,a protein previously proven to attenuate autophagy,can be considered an important reason for reducing autophagy and inflammation.In general,the carboxyl modification of SPIO nanoparticles has been demonstrated to reduce inflammation by inhibiting macrophage autophagy,which may provide some insights for the design of nanomaterials in the future.
基金supported by National Natural Science Foundation of China(NSFC,No.51903174 and 52073192)Innovative Research Groups of the National Natural Science Foundation of China(81621003).
文摘The T_(1)-T_(2) dual-mode probes for magnetic resonance imaging(MRI)can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same time,making MRI a more flexible imaging modality for complicated applications.In this work,three Gadolinium-diethylene-triaminepentaaceticacid(Gd-DTPA)complex conjugated superparamagnetic iron oxide(SPIO)nanoparticles with different Gd/Fe molar ratio(0.94,1.28 and 1.67)were prepared as T_(1)-T_(2) dual-mode MRI probes,named as SPIO@PEG-GdDTPA0.94,SPIO@PEGGdDTPA1.28 and SPIO@PEG-GdDTPA1.67,respectively.All SPIO@PEG-GdDTPA nanocomposites with 8 nm spherical SPIO nanocrystals showed good Gd3þchelate stability.SPIO@PEG-GdDTPA0.94 nanocomposites with lowest Gd/Fe molar ratio show no cytotoxicity to Raw 264.7 cells as compared to SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67.SPIO@PEG-GdDTPA0.94 nanocomposites with r1(8.4mM^(-1)s^(-1)),r2(83.2mM^(-1)s^(-1))and relatively ideal r2/r1 ratio(9.9)were selected for T_(1)-T_(2) dual-mode MRI of blood vessels and liver tissue in vivo.Good contrast images were obtained for both cardiovascular system and liver in animal studies under a clinical 3 T scanner.Importantly,one can get high-quality contrast-enhanced blood vessel images within the first 2 h after contrast agent administration and acquire liver tissue anatomy information up to 24 h.Overall,the strategy of one shot of the dual mode MRI agent could bring numerous benefits not only for patients but also to the radiologists and clinicians,e.g.saving time,lowering side effects and collecting data of different organs sequentially.