Limitations of monolayer culture conditions have motivated scientists to explore new models that can recapitulate the architecture and function of human organs more accurately.Recent advances in the improvement of pro...Limitations of monolayer culture conditions have motivated scientists to explore new models that can recapitulate the architecture and function of human organs more accurately.Recent advances in the improvement of protocols have resulted in establishing three-dimensional(3D)organ-like architectures called‘organoids’that can display the characteristics of their corresponding real organs,including morphological features,functional activities,and personalized responses to specific pathogens.We discuss different organoid-based 3D models herein,which are classified based on their original germinal layer.Studies of organoids simulating the complexity of real tissues could provide novel platforms and opportunities for generating practical knowledge along with preclinical studies,including drug screening,toxicology,and molecular pathophysiology of diseases.This paper also outlines the key challenges,advantages,and prospects of current organoid systems.展开更多
Multicellular microtissues of primary human hepatocytes(PHHs)co-cultured with other supporting cell types are a promis-ing model for drug screening and toxicological studies.However,these liver microtissues(LMs)rapidl...Multicellular microtissues of primary human hepatocytes(PHHs)co-cultured with other supporting cell types are a promis-ing model for drug screening and toxicological studies.However,these liver microtissues(LMs)rapidly lose their functions during ex vivo culture.Here,in order to mimic the cellular and structural hepatic microenvironment,we co-cultured PHHs with human mesenchymal stromal cells(MSCs)and human umbilical vein endothelial cells(HUVECs)in the presence of cell-sized microparticles(MPs)derived from liver extracellular matrix(LEMPs).The microwell culture platform enabled biofabrication of size-controlled multicellular microtissues(PHH:HUVEC:MSC=3:2:1)with efficient LEMP incorporation(about 70%at a 2:1 ratio of cells:MP).The biofabricated liver microtissues(BLMs)were cultured ex vivo for 14 days and compared to the cell-only LM in terms of gene and protein expression,functional activity,cytochrome P450(CYP450)enzyme inducibility,and drug sensitivity.The results supported superior hepatic-related gene expression,functional activity,and polarity for PHH in BLM compared to LM.CYP450 enzyme inducibility and dose-responsive sensitivity to toxic drugs were significantly higher in the BLM group.In conclusion,microtissue engineering by incorporation of tissue-specific microparticles within a multicellular microtissue can offer some advantages for drug discovery studies and cell transplantation applications.In the near future,this approach could generate a scalable platform of several functional biofabricated microtissues representing different organs.展开更多
Glioblastoma(GBM)is one of the most aggressive(grade IV)gliomas characterized by a high rate of recurrence,resistance to therapy and a grim survival prognosis.The long-awaited improvement in GBM patients'survival ...Glioblastoma(GBM)is one of the most aggressive(grade IV)gliomas characterized by a high rate of recurrence,resistance to therapy and a grim survival prognosis.The long-awaited improvement in GBM patients'survival rates essentially depends on advances in the development of new therapeutic approaches.Recent preclinical studies show that nanoscale materials could greatly contribute to the improvement of diagnosis and management of brain cancers.In the current review,we will discuss how specific features of glioma pathobiology can be employed for designing efficient targeting approaches.Moreover,we willsummarize the main evidence for the potential of the IL-13R alpha 2 receptor(IL13α2R)targeting in GBM early diagnosis and experimental therapy.展开更多
The efficiency of devices for bioelectronic applications,including cell and tissue stimulation,is heavily dependent on the scale and the performance level.With miniaturization of stimulation electrodes,achieving a suf...The efficiency of devices for bioelectronic applications,including cell and tissue stimulation,is heavily dependent on the scale and the performance level.With miniaturization of stimulation electrodes,achieving a sufficiently high current pulse to elicit action potentials becomes an issue.Herein we report on our approach of vertically stacking organic p-n junctions to create highlyefficient multilayered organic semiconductor(MOS)photostimulation device.A tandem arrangement substantially increases the photovoltage and charge density without sacrificing lateral area,while not exceeding 200-500 nm of thickness.These devices generate 4 times higher voltages and at least double the charge densities over single p-n junction devices,which allow using lower light intensities for stimulation.MOS devices show an outstanding stability in the electrolyte that is extremely important for forthcoming in vivo experiments.Finally,we have validated MOS devices performance by photostimulating fibroblasts and neuroblasts,and found that using tandem devices leads to more effective action potential generation.As a result,we obtained up to 4 times enhanced effect in cell growth density using 3 p-n layered devices.These results corroborate the conclusion that MOS technology not only can achieve parity with state-of-the-art silicon devices,but also can exceed them in miniaturization and performance for biomedical applications.展开更多
Intelligent drug delivery system based on “stimulus-response”mode emerging a promising perspective in next generation lipidbased nanoparticle.Here,we classify signal sources into physical and physiological stimulati...Intelligent drug delivery system based on “stimulus-response”mode emerging a promising perspective in next generation lipidbased nanoparticle.Here,we classify signal sources into physical and physiological stimulation according to their origin.展开更多
Ferritin has been widely used in drug delivery in recent years due to its unique spherical nanocage structure.In addition,the natural targeting and good biocompatibility of ferritin make it an excellent drug delivery ...Ferritin has been widely used in drug delivery in recent years due to its unique spherical nanocage structure.In addition,the natural targeting and good biocompatibility of ferritin make it an excellent drug delivery system.Therefore,ferritin has shown a broad application prospect in the field of nanomedicine.In this perspective,we will describe ferritin-based drug delivery system,ferritin-based drug delivery system for tumor treatment,and future challenges in ferritin development.Hopefully,this perspective may inspire the future development of ferritin-based drug delivery systems for tumor treatment.展开更多
基金supported by the National Cancer Control Charity Foundation(Registration Number 41476,Grant Number,235)Iran National Science Foundation,INSF(Grant Number,97014445)by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers"Digital biodesign and personalized healthcare"(No.075-15-2020-926).
文摘Limitations of monolayer culture conditions have motivated scientists to explore new models that can recapitulate the architecture and function of human organs more accurately.Recent advances in the improvement of protocols have resulted in establishing three-dimensional(3D)organ-like architectures called‘organoids’that can display the characteristics of their corresponding real organs,including morphological features,functional activities,and personalized responses to specific pathogens.We discuss different organoid-based 3D models herein,which are classified based on their original germinal layer.Studies of organoids simulating the complexity of real tissues could provide novel platforms and opportunities for generating practical knowledge along with preclinical studies,including drug screening,toxicology,and molecular pathophysiology of diseases.This paper also outlines the key challenges,advantages,and prospects of current organoid systems.
基金supported by Grants from Royan Institute(No.96000165)to MV and HBBahar Tashkhis Teb Co.(Nos.BTT,9702,and 9802)+1 种基金Iran National Science Foundation(No.97014445)to MVthe Ministry of Health and Medical Education(No.56700/147)to HB.
文摘Multicellular microtissues of primary human hepatocytes(PHHs)co-cultured with other supporting cell types are a promis-ing model for drug screening and toxicological studies.However,these liver microtissues(LMs)rapidly lose their functions during ex vivo culture.Here,in order to mimic the cellular and structural hepatic microenvironment,we co-cultured PHHs with human mesenchymal stromal cells(MSCs)and human umbilical vein endothelial cells(HUVECs)in the presence of cell-sized microparticles(MPs)derived from liver extracellular matrix(LEMPs).The microwell culture platform enabled biofabrication of size-controlled multicellular microtissues(PHH:HUVEC:MSC=3:2:1)with efficient LEMP incorporation(about 70%at a 2:1 ratio of cells:MP).The biofabricated liver microtissues(BLMs)were cultured ex vivo for 14 days and compared to the cell-only LM in terms of gene and protein expression,functional activity,cytochrome P450(CYP450)enzyme inducibility,and drug sensitivity.The results supported superior hepatic-related gene expression,functional activity,and polarity for PHH in BLM compared to LM.CYP450 enzyme inducibility and dose-responsive sensitivity to toxic drugs were significantly higher in the BLM group.In conclusion,microtissue engineering by incorporation of tissue-specific microparticles within a multicellular microtissue can offer some advantages for drug discovery studies and cell transplantation applications.In the near future,this approach could generate a scalable platform of several functional biofabricated microtissues representing different organs.
基金This work was financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers"Digital Biodesign and Personalized Healthcare"(No.075-15-2020-926).
文摘Glioblastoma(GBM)is one of the most aggressive(grade IV)gliomas characterized by a high rate of recurrence,resistance to therapy and a grim survival prognosis.The long-awaited improvement in GBM patients'survival rates essentially depends on advances in the development of new therapeutic approaches.Recent preclinical studies show that nanoscale materials could greatly contribute to the improvement of diagnosis and management of brain cancers.In the current review,we will discuss how specific features of glioma pathobiology can be employed for designing efficient targeting approaches.Moreover,we willsummarize the main evidence for the potential of the IL-13R alpha 2 receptor(IL13α2R)targeting in GBM early diagnosis and experimental therapy.
基金funded by the Ministry of Science and Higher Education of the Russian Federation(No.075-15-2021-596).
文摘The efficiency of devices for bioelectronic applications,including cell and tissue stimulation,is heavily dependent on the scale and the performance level.With miniaturization of stimulation electrodes,achieving a sufficiently high current pulse to elicit action potentials becomes an issue.Herein we report on our approach of vertically stacking organic p-n junctions to create highlyefficient multilayered organic semiconductor(MOS)photostimulation device.A tandem arrangement substantially increases the photovoltage and charge density without sacrificing lateral area,while not exceeding 200-500 nm of thickness.These devices generate 4 times higher voltages and at least double the charge densities over single p-n junction devices,which allow using lower light intensities for stimulation.MOS devices show an outstanding stability in the electrolyte that is extremely important for forthcoming in vivo experiments.Finally,we have validated MOS devices performance by photostimulating fibroblasts and neuroblasts,and found that using tandem devices leads to more effective action potential generation.As a result,we obtained up to 4 times enhanced effect in cell growth density using 3 p-n layered devices.These results corroborate the conclusion that MOS technology not only can achieve parity with state-of-the-art silicon devices,but also can exceed them in miniaturization and performance for biomedical applications.
基金This work was supported by Beijing Natural Science Foundation(7214283)the National Key Research&Development Program of China(grant Nos.2021YFA1201000 and 2018YFE0117800)+3 种基金National Natural Science Foundation of China(NSFC)Key Project(grant No.32030060)NSFC International CollaborationKey Project(grant No.51861135103)The authors also appreciate the support by the Beijing-Tianjin-Hebei Basic Research Cooperation Project(19JCZDJC64100)This study was also supported by the Science and Technology Development Fund,Macao SAR(File no.0124/2019/A3).
文摘Intelligent drug delivery system based on “stimulus-response”mode emerging a promising perspective in next generation lipidbased nanoparticle.Here,we classify signal sources into physical and physiological stimulation according to their origin.
基金Ministry of Science and Higher Education of the Russian Federation,Grant/Award Number:075-15-2021-596Science Fund for Creative Research Groups of Nature Science Foundation of Hebei Province,Grant/Award Number:B2021201038+3 种基金National Key Research&Development Program of China,Grant/Award Numbers:2021YFA1201000,2018YFE0117800the Beijing-Tianjin-Hebei Basic Research Cooperation Project,Grant/Award Number:19JCZDJC64100NSFC international collaboration,Grant/Award Number:51861135103National Natural Science Foundation of China,Grant/Award Numbers:32030060,82202336。
文摘Ferritin has been widely used in drug delivery in recent years due to its unique spherical nanocage structure.In addition,the natural targeting and good biocompatibility of ferritin make it an excellent drug delivery system.Therefore,ferritin has shown a broad application prospect in the field of nanomedicine.In this perspective,we will describe ferritin-based drug delivery system,ferritin-based drug delivery system for tumor treatment,and future challenges in ferritin development.Hopefully,this perspective may inspire the future development of ferritin-based drug delivery systems for tumor treatment.
