Successful cancer therapy depends on selective killing of tumor cells while sparing normal cells. Selectivity can be achieved through treatment strategies that target tumor cells. A recent report from the Li laborato...Successful cancer therapy depends on selective killing of tumor cells while sparing normal cells. Selectivity can be achieved through treatment strategies that target tumor cells. A recent report from the Li laboratory (1) describes an elegant strategy to selectively kill tumor cells by combining several targeting strategies based on cell biological, physical, and molecular (genetic) properties of tumor and normal cells that enhances tumor cell killing in vitro and in an in vivo tumor xenograft model. The idea of using a multiplex targeting approach is reminiscent of strategies in which several antibiotics are used to treat bacterial infections while minimizing the chance that rare antibiotic-resistant mutants will arise within a population.展开更多
Alzheimer's disease (AD) is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the dis...Alzheimer's disease (AD) is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the disease progresses, AD inevitably affects all intellectual functions including executive functions, leading to complete dependence for basic activities of daily life and premature death.展开更多
Neurodegeneration is characterized by the progressive and permanent loss of neurons.Degeneration typically results in a debilitating loss of function in an otherwise healthy person.Neurodegenerative diseases have enor...Neurodegeneration is characterized by the progressive and permanent loss of neurons.Degeneration typically results in a debilitating loss of function in an otherwise healthy person.Neurodegenerative diseases have enormous direct health care costs,with some estimates for diseases.展开更多
Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify onco...Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto展开更多
Cancer stem cells(CSCs)are a subpopulation of cancer cells with functions similar to those of normal stem cells.Although few in number,they are capable of self-renewal,unlimited proliferation,and multi-directional dif...Cancer stem cells(CSCs)are a subpopulation of cancer cells with functions similar to those of normal stem cells.Although few in number,they are capable of self-renewal,unlimited proliferation,and multi-directional differentiation potential.In addition,CSCs have the ability to escape immune surveillance.Thus,they play an important role in the occurrence and development of tumors,and they are closely related to tumor invasion,metastasis,drug resistance,and recurrence after treatment.Therefore,specific targeting of CSCs may improve the efficiency of cancer therapy.A series of corresponding promising therapeutic strategies based on CSC targeting,such as the targeting of CSC niche,CSC signaling pathways,and CSC mitochondria,are currently under development.Given the rapid progression in this field and nanotechnology,drug delivery systems(DDSs)for CSC targeting are increasingly being developed.In this review,we summarize the advances in CSC-targeted DDSs.Furthermore,we highlight the latest developmental trends through the main line of CSC occurrence and development process;some considerations about the rationale,advantages,and limitations of different DDSs for CSCtargeted therapies were discussed.展开更多
Acute respiratory distress syndrome(ARDS)is characterized by the severe inflammation and destruction of the lung aireblood barrier,leading to irreversible and substantial respiratory function damage.Patients with coro...Acute respiratory distress syndrome(ARDS)is characterized by the severe inflammation and destruction of the lung aireblood barrier,leading to irreversible and substantial respiratory function damage.Patients with coronavirus disease 2019(COVID-19)have been encountered with a high risk of ARDS,underscoring the urgency for exploiting effective therapy.However,proper medications for ARDS are still lacking due to poor pharmacokinetics,non-specific side effects,inability to surmount pulmonary barrier,and inadequate management of heterogeneity.The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery.Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy,which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment.Through passive,active,or physicochemical targeting,nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment,thereby showing good therapeutic activity and reduced toxicity.This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy,highlights the strategies for targeted treatment of lung inflammation,presents the innovative drug delivery systems,and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.展开更多
Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent bioc...Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.展开更多
Cancer is one of the most fatal diseases for decades.Aggregation-induced emission luminogens(AIEgens)have been recently used as molecular imaging or therapeutic agents in cancers,due to the advantages of large Stokes ...Cancer is one of the most fatal diseases for decades.Aggregation-induced emission luminogens(AIEgens)have been recently used as molecular imaging or therapeutic agents in cancers,due to the advantages of large Stokes shift,high quantum yield,great biocompatibility,and strong photostability.AIEgens can specifically target different types of cancer via diverse targeting strategies.AIEgen-based fluorescence imaging,especially near-infrared imaging,demonstrated deep penetration and suitable signal-to-noise ratio,which allows reliable in vivo cancer imaging.Combined with other imaging modalities,AIEgen-based multimodal imaging could provide multidimensional cancer hallmarks from different perspectives.In addition,AIEgenbased phototherapy can be used for photodynamic therapy and photothermal therapy,which facilitate ablation of cancer cells with good biosafety and high therapeutic effects in vivo.AIEgens nanoparticles fabricated with some specific chemicals,drugs,or siRNA,could display synergistic therapeutic effects for cancers.This paper comprehensively describes the current status and future perspectives of AIEgens,which have showed a great potential for the future preclinical and clinical translation on in vivo molecular imaging and theranostics in cancer.展开更多
Incorporating metal nanodots(NDs)into heterostructures for high charge separation and transfer capacities is one of the most effective strategies for improving their photocatalytic activities.However,controlling the s...Incorporating metal nanodots(NDs)into heterostructures for high charge separation and transfer capacities is one of the most effective strategies for improving their photocatalytic activities.However,controlling the space distribution of metal NDs for optimizing charge transport pathways remains a significant challenge,particularly in two-dimensional(2D)face-to-face heterostructures.Herein,we develop a simple targeted self-reduction strategy for selectively loading Ru NDs onto the Ti_(3−x)C_(2)T_(y)(TC)surface of 2D TC/g-C_(3)N_(4)(CN)heterojunction based on the reductive Ti vacancy defects creatively increased during the preparation of TC/CN by reducing calcination.Notably,the optimized Ru/TC/CN photocatalyst exhibits an outstanding H_(2)evolution rate of 3.21 mmol·g^(−1)·h^(−1)and a high apparent quantum efficiency of 30.9%at 380 nm,which is contributed by the unidirectional transfer of the photogenerated electrons from CN to Ru active sites(CN→TC→Ru)and the suppressed backflow of electrons from Ru sites to CN,as revealed by comprehensive characterizations and density functional theory(DFT)calculations.This work provides a novel strategy for synthesizing the highly efficient photocatalysts with a controllable charge transfer paths,which will boost the development of photocatalysis.展开更多
T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell progenitors.The development of targeted therapeutic regimens is impeded by poo...T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell progenitors.The development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this disease.In this study,we performed multi-omics integration analysis,which included mRNA expression,chromatin accessibility,and gene-dependency database analyses,to identify potential stage-specific druggable targets and repositioned drugs for this disease.This multi-omics integration helped identify 29 potential pathological genes for T-ALL.These genes exhibited tissue-specific expression profiles and were enriched in the cell cycle,hematopoietic stem cell differentiation,and the AMPK signaling pathway.Of these,four known druggable targets(CDK6,TUBA1A,TUBB,and TYMS)showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in T-ALL.The TUBA1A expression level was higher in the early T cell precursor(ETP)-ALL cells,while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive stage.CDK6 exhibited a U-shaped expression pattern in malignant T cells along the naıve to maturation stages.Furthermore,mebendazole and gemcitabine,which target TUBA1A and TYMS,respectively,exerted stage-specific inhibitory effects on T-ALL cell lines,indicating their potential stage-specific antileukemic role in T-ALL.Collectively,our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.展开更多
基金supported by NIH grant R01 GM084020the Japan National Institute of Radiological Sciences International Open Laboratory Program
文摘Successful cancer therapy depends on selective killing of tumor cells while sparing normal cells. Selectivity can be achieved through treatment strategies that target tumor cells. A recent report from the Li laboratory (1) describes an elegant strategy to selectively kill tumor cells by combining several targeting strategies based on cell biological, physical, and molecular (genetic) properties of tumor and normal cells that enhances tumor cell killing in vitro and in an in vivo tumor xenograft model. The idea of using a multiplex targeting approach is reminiscent of strategies in which several antibiotics are used to treat bacterial infections while minimizing the chance that rare antibiotic-resistant mutants will arise within a population.
文摘Alzheimer's disease (AD) is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the disease progresses, AD inevitably affects all intellectual functions including executive functions, leading to complete dependence for basic activities of daily life and premature death.
文摘Neurodegeneration is characterized by the progressive and permanent loss of neurons.Degeneration typically results in a debilitating loss of function in an otherwise healthy person.Neurodegenerative diseases have enormous direct health care costs,with some estimates for diseases.
文摘Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto
基金supported by the Drug Innovation Major Project(2018ZX09711001-002-005,China)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2017-I2M-1-011,China)+1 种基金National Natural Science Foundation of China(No.82073778,China)Fundamental Research Funds for the Central Public Welfare Research Institutes(2018PT35002,China)
文摘Cancer stem cells(CSCs)are a subpopulation of cancer cells with functions similar to those of normal stem cells.Although few in number,they are capable of self-renewal,unlimited proliferation,and multi-directional differentiation potential.In addition,CSCs have the ability to escape immune surveillance.Thus,they play an important role in the occurrence and development of tumors,and they are closely related to tumor invasion,metastasis,drug resistance,and recurrence after treatment.Therefore,specific targeting of CSCs may improve the efficiency of cancer therapy.A series of corresponding promising therapeutic strategies based on CSC targeting,such as the targeting of CSC niche,CSC signaling pathways,and CSC mitochondria,are currently under development.Given the rapid progression in this field and nanotechnology,drug delivery systems(DDSs)for CSC targeting are increasingly being developed.In this review,we summarize the advances in CSC-targeted DDSs.Furthermore,we highlight the latest developmental trends through the main line of CSC occurrence and development process;some considerations about the rationale,advantages,and limitations of different DDSs for CSCtargeted therapies were discussed.
基金supported by the National Natural Science Foundation of China(81872810)Program for HUST Academic Frontier Youth Team(2018QYTD13,China)the Fundamental Research Funds for the Central Universities(2018KFYYXJJ019 and 2019KFYRCPY049,China)。
文摘Acute respiratory distress syndrome(ARDS)is characterized by the severe inflammation and destruction of the lung aireblood barrier,leading to irreversible and substantial respiratory function damage.Patients with coronavirus disease 2019(COVID-19)have been encountered with a high risk of ARDS,underscoring the urgency for exploiting effective therapy.However,proper medications for ARDS are still lacking due to poor pharmacokinetics,non-specific side effects,inability to surmount pulmonary barrier,and inadequate management of heterogeneity.The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery.Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy,which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment.Through passive,active,or physicochemical targeting,nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment,thereby showing good therapeutic activity and reduced toxicity.This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy,highlights the strategies for targeted treatment of lung inflammation,presents the innovative drug delivery systems,and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.
基金supported by the grants from University of Macao,China,Nos.MYRG2022-00221-ICMS(to YZ)and MYRG-CRG2022-00011-ICMS(to RW)the Natural Science Foundation of Guangdong Province,No.2023A1515010034(to YZ)。
文摘Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.
基金National Natural Science Foundation of China,Grant/Award Numbers:21788102,32027802Key R&D Program of Zhejiang,Grant/Award Number:2022C03071Fundamental Research Funds for the Central Universities。
文摘Cancer is one of the most fatal diseases for decades.Aggregation-induced emission luminogens(AIEgens)have been recently used as molecular imaging or therapeutic agents in cancers,due to the advantages of large Stokes shift,high quantum yield,great biocompatibility,and strong photostability.AIEgens can specifically target different types of cancer via diverse targeting strategies.AIEgen-based fluorescence imaging,especially near-infrared imaging,demonstrated deep penetration and suitable signal-to-noise ratio,which allows reliable in vivo cancer imaging.Combined with other imaging modalities,AIEgen-based multimodal imaging could provide multidimensional cancer hallmarks from different perspectives.In addition,AIEgenbased phototherapy can be used for photodynamic therapy and photothermal therapy,which facilitate ablation of cancer cells with good biosafety and high therapeutic effects in vivo.AIEgens nanoparticles fabricated with some specific chemicals,drugs,or siRNA,could display synergistic therapeutic effects for cancers.This paper comprehensively describes the current status and future perspectives of AIEgens,which have showed a great potential for the future preclinical and clinical translation on in vivo molecular imaging and theranostics in cancer.
基金the National Natural Science Foundation of China(No.22002142)China Postdoctoral Science Foundation(No.2020T130605)+2 种基金Natural Science Foundation of Henan Province(No.202300410436)Support Plan for College Science and Technology Innovation Team of Henan Province(No.16IRTSTHN001)the Science&Technology Innovation Talent Plan of Henan Province(No.174200510018).
文摘Incorporating metal nanodots(NDs)into heterostructures for high charge separation and transfer capacities is one of the most effective strategies for improving their photocatalytic activities.However,controlling the space distribution of metal NDs for optimizing charge transport pathways remains a significant challenge,particularly in two-dimensional(2D)face-to-face heterostructures.Herein,we develop a simple targeted self-reduction strategy for selectively loading Ru NDs onto the Ti_(3−x)C_(2)T_(y)(TC)surface of 2D TC/g-C_(3)N_(4)(CN)heterojunction based on the reductive Ti vacancy defects creatively increased during the preparation of TC/CN by reducing calcination.Notably,the optimized Ru/TC/CN photocatalyst exhibits an outstanding H_(2)evolution rate of 3.21 mmol·g^(−1)·h^(−1)and a high apparent quantum efficiency of 30.9%at 380 nm,which is contributed by the unidirectional transfer of the photogenerated electrons from CN to Ru active sites(CN→TC→Ru)and the suppressed backflow of electrons from Ru sites to CN,as revealed by comprehensive characterizations and density functional theory(DFT)calculations.This work provides a novel strategy for synthesizing the highly efficient photocatalysts with a controllable charge transfer paths,which will boost the development of photocatalysis.
基金the National Natural Science Foundation of China(No.82070167,81870126,81900190,81802803)The Chongqing Science and Technology Bureau Major Project,Chongqing,China(No.cstc2020jcyjmsxmX0782).
文摘T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell progenitors.The development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this disease.In this study,we performed multi-omics integration analysis,which included mRNA expression,chromatin accessibility,and gene-dependency database analyses,to identify potential stage-specific druggable targets and repositioned drugs for this disease.This multi-omics integration helped identify 29 potential pathological genes for T-ALL.These genes exhibited tissue-specific expression profiles and were enriched in the cell cycle,hematopoietic stem cell differentiation,and the AMPK signaling pathway.Of these,four known druggable targets(CDK6,TUBA1A,TUBB,and TYMS)showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in T-ALL.The TUBA1A expression level was higher in the early T cell precursor(ETP)-ALL cells,while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive stage.CDK6 exhibited a U-shaped expression pattern in malignant T cells along the naıve to maturation stages.Furthermore,mebendazole and gemcitabine,which target TUBA1A and TYMS,respectively,exerted stage-specific inhibitory effects on T-ALL cell lines,indicating their potential stage-specific antileukemic role in T-ALL.Collectively,our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.