The tumor microenvironment(TME)-activatable probes have proven effective in enhancing the signalto-background ratio(SBR)for precise fluorescence imaging in tumor diagnosis.However,many fluorophores have suboptimal emi...The tumor microenvironment(TME)-activatable probes have proven effective in enhancing the signalto-background ratio(SBR)for precise fluorescence imaging in tumor diagnosis.However,many fluorophores have suboptimal emission spectra and a short Stokes shift,which may lead to overlap with bioautofluorescence,excitation,and emission spectra,limiting their use in intraoperative guidance.Herein,aγ-glutathione(GSH)responsive near-infrared(NIR)BODIPY probe,named“Pro-Dye”was synthesized with a large Stokes shift of 91 nm.The Pro-Dye can be rapidly and specifically activated by high concentrations of GSH both in solution and inside cancer cells,while remaining inactive in normal cells(Human umbilical vein endothelial cells,HUVECs).The Pro-Dye was further encapsulated by 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(polyethylene glycol)-5000(DSPE-PEG5000)to form Pro-Dye nanoparticles(NPs),making it water-dispersible for in vivo application.In vivo fluorescence imaging demonstrated that Pro-Dye NPs can accumulate at the tumor and exhibit an improved SBR compared to the“alwayson”probe(Dye NPs).Moreover,the tumor can be precisely resected under the real-time guidance of fluorescence imaging of Pro-Dye NPs,showing a well-defined tumor margin.展开更多
Colorectal cancer(CRC)is the most common gastrointestinal tract cancer worldwide and is associated with high morbidity and mortality.The development of nanosized drug delivery systems has provided a new direction in C...Colorectal cancer(CRC)is the most common gastrointestinal tract cancer worldwide and is associated with high morbidity and mortality.The development of nanosized drug delivery systems has provided a new direction in CRC treatment.Among these systems,magnetic nanoparticle(MNP)-based multifunctional platforms provide a novel strategy for magnetic resonance imaging(MRI)-related cancer theranostics.At the beginning o f this original review,the carcinogenesis and treatment status o f CRC are summarized.Then,diversified preparation and functionalization methods of MNPs are systematically analyzed,followed by MRIinvolved theranostic strategies.The latest progress in MRI-mediated multimode diagnosis and image-guided targeted therapy in CRC management is the main focus.Finally,the major challenges in promoting MRI-induced precise theranostics of CRC in clinical practice are discussed.展开更多
The tumor microenvironment(TME)significantly influences cancer evolution and therapeutic efficacy.Targeting biofunctional molecules to the TME has long been appreciated as a means of raising local drug concentrations ...The tumor microenvironment(TME)significantly influences cancer evolution and therapeutic efficacy.Targeting biofunctional molecules to the TME has long been appreciated as a means of raising local drug concentrations and reducing systemic toxicities.The booming nanotechnology field has realized the importance of cathepsin B to derive a variety of intelligent enzyme-responsive nanosized drug delivery systems(nanoDDS)to improve treatment responses and clinical outcomes.In this tutorial review,after introducing the molecular structure and physiological/pathological functions of cathepsin B,the outstanding achievements of cathepsin B-responsive nanoplatforms in the precise diagnosis,targeted therapy,and synergistic theranostics of malignant tumors are systematically described.Finally,the challenges of enzyme-substrate incompatibility,low diagnostic sensitivity,mass production and biocompatibility of multifunctional nanoDDS are considered in order to successfully promote them to clinical applications.展开更多
Tumor microenvironment(TME)-activatable probes have been proven to effectively increase signal-tobackground ratios(SBRs)and improve the success rate of complete tumor resection.However,many fluorescence probes have to...Tumor microenvironment(TME)-activatable probes have been proven to effectively increase signal-tobackground ratios(SBRs)and improve the success rate of complete tumor resection.However,many fluorescence probes have to be loaded into a nanocarrier for tumor targeted delivery,which consequently encounters poor drug loading,heterogeneous composition and non-encapsulated drug aggregates occurred during nanoformulation fabrications.Herein,a nitroreductase(NTR)-activated“OFF-ON”near-infrared fluorescence nanoprobe,named Nano Bodipy,was synthesized by the spontaneous self-assembling of NTRresponsive dye-polyethylene glycol(PEG)amphiphilic polymer in water.The NTR-responsive dye acted as the hydrophobic segment in the amphiphilic polymer,yielding a homogeneous composition and a high loading of 12.2 wt%(according to calculation)in the synthesized Nano Bodipy.The synthesized Nano Bodipy can efficiently accumulate in tumors via the enhanced permeability and retention(EPR)effect,enabling non-invasive tumor-targeted fluorescence imaging and guiding complete tumor resection.Once the synthesized Nano Bodipy entered the tumor cells,they dissociated and were activated by overexpressed NTR.With the real-time fluorescence guide of Nano Bodipy,complete tumor resection surgery was performed successfully.展开更多
Photoimmunotherapy is an emerging treatment modality that uses photothermal,photodynamic and photochemical processes to fight against cancer by eliciting a robust host immune response.Recently,various nanoformulations...Photoimmunotherapy is an emerging treatment modality that uses photothermal,photodynamic and photochemical processes to fight against cancer by eliciting a robust host immune response.Recently,various nanoformulations of biomaterials have been rationally designed as highly effective photosensitive agents,immunoadjuvants or carriers to enhance phototherapeutic efficacy,boost immune stimulation,amplify nano-permeability and monitor cancer progression in situ.Nevertheless,relying solely on a single-modality therapy may not completely ablate primary tumors,and the metastasis and recurrence of tumors remain a serious challenge.To solve this issue,the strategy of combining photoimmunotherapy with other immunotherapies,such as immune checkpoint blockade,chimeric antigen receptor-T cell or cytokine therapy,can greatly enhance the effectiveness of oncology treatment and reduce the traditional adverse effects.Thus,it is very valuable to summarize the research progress in biomaterial-assisted combination photoimmunotherapy for clinical translation.In this review,the recent advances in constructing multifunctional nano-biomaterials for combinatorial photoimmunotherapy of cancer are summarized.Furthermore,the opportunities,challenges,future trends and prospects in this field are also analyzed to pave the way for advancing the next generation of clinical cancer management strategies.展开更多
Sonodynamic therapy(SDT)is an innovative cancer therapy modality that harnesses the energy of ultrasound to activate sonosensitizers for producing reactive oxygen species(ROS),culminating in the eradication of tumor c...Sonodynamic therapy(SDT)is an innovative cancer therapy modality that harnesses the energy of ultrasound to activate sonosensitizers for producing reactive oxygen species(ROS),culminating in the eradication of tumor cells.Compared with photodynamic therapy,SDT has the capacity to penetrate deeply into biological tissues,thereby holding significant promise for addressing deeply situated or surgically inaccessible tumors.The effectiveness of SDT is greatly dependent on the characteristics of the sonosensitizers,and unlike inorganic sonosensitizers,organic sonosensitizers offer a more controlled synthesis process and have excellent biocompatibility.This review presents ameticulous undertaking to categorize organic sonosensitizers and elucidate theirmechanisms of action and therapeutic effects in the context of SDT.Design strategies for sonosensitizers are also summarized,and we emphasize the critical role of nanotechnology in tumor localization,imaging,and multimodal synergistic therapy,offering an innovative approach for achieving precise tumor targeting.In addition,the synergistic impact of SDT is delineated when integrated with other oncological modalities,such as photothermal therapy and photodynamic therapy,to enhance therapeutic efficacy.Finally,the review also discusses challenges and future perspectives for the advancement of clinical SDT within the realm of oncology.展开更多
Proteases have a fundamental role in maintaining physiological homeostasis,but their dysregulation results in severe activity imbalance and pathological conditions,including cancer onset,progression,invasion,and metas...Proteases have a fundamental role in maintaining physiological homeostasis,but their dysregulation results in severe activity imbalance and pathological conditions,including cancer onset,progression,invasion,and metastasis.This striking importance plus superior biological recognition and catalytic performance of proteases,combining with the excellent physicochemical characteristics of nanomaterials,results in enzyme-activated nano-drug delivery systems(nanoDDS)that perform theranostic functions in highly specific response to the tumor phenotype stimulus.In the tutorial review,the key advances of protease-responsive nanoDDS in the specific diagnosis and targeted treatment for malignancies are emphatically classified according to the effector biomolecule types,on the premise of summarizing the structure and function of each protease.Subsequently,the incomplete matching and recognition between enzyme and substrate,structural design complexity,volume production,and toxicological issues related to the nanocomposites are highlighted to clarify the direction of efforts in nanotheranostics.This will facilitate the promotion of nanotechnology in the management of malignant tumors.展开更多
Fluorescent analysis of bone provides valuable insights into bone structures.However,conventional dyes suffer from low specificity on bone tissue,small stokes shift,short fluorescent lifetime,and aggregation-caused qu...Fluorescent analysis of bone provides valuable insights into bone structures.However,conventional dyes suffer from low specificity on bone tissue,small stokes shift,short fluorescent lifetime,and aggregation-caused quenching effect,which result in low efficacy and artifacts.In this work,we design an aggregation-induced emission(AIE)-active iridium(III)complex(Ir-BP2)as a highly selective,convenient,nondestructiveness,and dual-mode staining agent for bone analysis.Ir-BP2 containing phosphonate groups selectively binds to hydroxyapatites,the main component of bone matrix,and exhibits turn-on AIE phosphorescence with prolonged lifetime.Ir-BP2 exhibits promising biosafety and offers higher accuracy in staining calcium deposits than conventional Alizarin Red S staining assay when it is employed in real-time monitoring of osteogenesis differentiation process.A ready-to-use staining spray of Ir-BP2 is fabricated.By using fluorescent imaging and lifetime imaging,Ir-BP2 staining provides valuable insights into bone microstructure analysis,microdamage diagnosis,and bone growth state identification.Further,Ir-BP2 is successfully applied on a human spine vertebra for diagnosing bone invasiveness of eosinophilic granuloma,validating its clinical practice.This work presents a powerful tool in bone analysis and will lead to new approaches for the diagnosis and treatment of bone-related diseases.展开更多
Dear Editor,Generation of heterozygous genomes by hybridization between or within species can help maintain plant diversity and serve as a potential source of new species(Baek et al.,2018).Moreover,genomic heterozygos...Dear Editor,Generation of heterozygous genomes by hybridization between or within species can help maintain plant diversity and serve as a potential source of new species(Baek et al.,2018).Moreover,genomic heterozygosity is associated with genomic coadaptation,developmental stability,and heterosis.Accurate definition of alleles in haplotypes is necessary to precisely characterize allelic variation controlling agriculturally important traits(Shi et al.,2019).Currently,most released genomes have mosaic assembly of haplotypes due to random selection or collapse of alleles during genome assembly(Shi et al.,2019),which masked allelic variation and functional differentiation of divergent alleles in heterozygous species.展开更多
基金supported by the Natural Science Foundation of Shaanxi Province(Nos.2023-YBSF-270,2024SF-ZDCYL-02-08)Fundamental Research Funds for the Central Universities(No.xzy022024033)+2 种基金Horizontal Project of the First Affiliated Hospital of Xi’an Jiaotong University(No.202304174)supported by the Opening Project of Structural Optimization and Application of Functional Molecules Key Laboratory of Sichuan Province(No.2023GNFZ-03)The Key Laboratory for Screening and Diagnosis of Maternal and Child Genetic Disease of Health Commission of Jiangxi Province.
文摘The tumor microenvironment(TME)-activatable probes have proven effective in enhancing the signalto-background ratio(SBR)for precise fluorescence imaging in tumor diagnosis.However,many fluorophores have suboptimal emission spectra and a short Stokes shift,which may lead to overlap with bioautofluorescence,excitation,and emission spectra,limiting their use in intraoperative guidance.Herein,aγ-glutathione(GSH)responsive near-infrared(NIR)BODIPY probe,named“Pro-Dye”was synthesized with a large Stokes shift of 91 nm.The Pro-Dye can be rapidly and specifically activated by high concentrations of GSH both in solution and inside cancer cells,while remaining inactive in normal cells(Human umbilical vein endothelial cells,HUVECs).The Pro-Dye was further encapsulated by 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(polyethylene glycol)-5000(DSPE-PEG5000)to form Pro-Dye nanoparticles(NPs),making it water-dispersible for in vivo application.In vivo fluorescence imaging demonstrated that Pro-Dye NPs can accumulate at the tumor and exhibit an improved SBR compared to the“alwayson”probe(Dye NPs).Moreover,the tumor can be precisely resected under the real-time guidance of fluorescence imaging of Pro-Dye NPs,showing a well-defined tumor margin.
基金the National Natural Science Foundation of China(Grant Nos.81903662,81860630,and 81560577)China Postdoctoral Science Foundation Grant(Grant No.2019M661057)+3 种基金the Applied Basic Research Programs of Shanxi Province(Grant No.201901D 211347)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(Grant No.2019L0428)the Startup Foundation for Doctors of Shanxi Province(Grant No.SD1827)the Startup Foundation for Doctors of Shanxi Medical University(Grant No.XD1824).
文摘Colorectal cancer(CRC)is the most common gastrointestinal tract cancer worldwide and is associated with high morbidity and mortality.The development of nanosized drug delivery systems has provided a new direction in CRC treatment.Among these systems,magnetic nanoparticle(MNP)-based multifunctional platforms provide a novel strategy for magnetic resonance imaging(MRI)-related cancer theranostics.At the beginning o f this original review,the carcinogenesis and treatment status o f CRC are summarized.Then,diversified preparation and functionalization methods of MNPs are systematically analyzed,followed by MRIinvolved theranostic strategies.The latest progress in MRI-mediated multimode diagnosis and image-guided targeted therapy in CRC management is the main focus.Finally,the major challenges in promoting MRI-induced precise theranostics of CRC in clinical practice are discussed.
基金the National Natural Science Foundation of China(Nos.81903662,51903201)China Postdoctoral Science Foundation Grant(Nos.2019M661057,2019M653660)+5 种基金the Applied Basic Research Programs of Shanxi Province(No.201901D211347)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2019L0428)the Startup Foundation for Doctors of Shanxi Province(No.SD1827)Natural Science Foundation of Shaanxi Province(No.2020JQ-086)College Students’Innovation and Entrepreneurship Training Program(No.SJ201910698121)the Startup Foundation for Doctors of Shanxi Medical University(No.XD1824)。
文摘The tumor microenvironment(TME)significantly influences cancer evolution and therapeutic efficacy.Targeting biofunctional molecules to the TME has long been appreciated as a means of raising local drug concentrations and reducing systemic toxicities.The booming nanotechnology field has realized the importance of cathepsin B to derive a variety of intelligent enzyme-responsive nanosized drug delivery systems(nanoDDS)to improve treatment responses and clinical outcomes.In this tutorial review,after introducing the molecular structure and physiological/pathological functions of cathepsin B,the outstanding achievements of cathepsin B-responsive nanoplatforms in the precise diagnosis,targeted therapy,and synergistic theranostics of malignant tumors are systematically described.Finally,the challenges of enzyme-substrate incompatibility,low diagnostic sensitivity,mass production and biocompatibility of multifunctional nanoDDS are considered in order to successfully promote them to clinical applications.
基金supported by the National Natural Science Foundation of China(Nos.51903201,82172798)the Natural Science Foundation of Shaanxi Province(No.2023-YBSF-270)+1 种基金the Open Program of NHC Key Laboratory of Nuclear Medicine and Jiangsu Key Laboratory of Molecular Nuclear Medicine(No.KF202203)Horizontal Project of the First Affiliated Hospital of Xi'an Jiaotong University(No.202304174)。
文摘Tumor microenvironment(TME)-activatable probes have been proven to effectively increase signal-tobackground ratios(SBRs)and improve the success rate of complete tumor resection.However,many fluorescence probes have to be loaded into a nanocarrier for tumor targeted delivery,which consequently encounters poor drug loading,heterogeneous composition and non-encapsulated drug aggregates occurred during nanoformulation fabrications.Herein,a nitroreductase(NTR)-activated“OFF-ON”near-infrared fluorescence nanoprobe,named Nano Bodipy,was synthesized by the spontaneous self-assembling of NTRresponsive dye-polyethylene glycol(PEG)amphiphilic polymer in water.The NTR-responsive dye acted as the hydrophobic segment in the amphiphilic polymer,yielding a homogeneous composition and a high loading of 12.2 wt%(according to calculation)in the synthesized Nano Bodipy.The synthesized Nano Bodipy can efficiently accumulate in tumors via the enhanced permeability and retention(EPR)effect,enabling non-invasive tumor-targeted fluorescence imaging and guiding complete tumor resection.Once the synthesized Nano Bodipy entered the tumor cells,they dissociated and were activated by overexpressed NTR.With the real-time fluorescence guide of Nano Bodipy,complete tumor resection surgery was performed successfully.
基金supported by the National Natural Science Foundation of China(Nos.81903662,51903201)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2019L0428)+1 种基金the Natural Science Foundation of Shaanxi Province(No.2023-YBSF-270)the Startup Foundation for Doctors of Shanxi Medical University(No.XD1824)。
文摘Photoimmunotherapy is an emerging treatment modality that uses photothermal,photodynamic and photochemical processes to fight against cancer by eliciting a robust host immune response.Recently,various nanoformulations of biomaterials have been rationally designed as highly effective photosensitive agents,immunoadjuvants or carriers to enhance phototherapeutic efficacy,boost immune stimulation,amplify nano-permeability and monitor cancer progression in situ.Nevertheless,relying solely on a single-modality therapy may not completely ablate primary tumors,and the metastasis and recurrence of tumors remain a serious challenge.To solve this issue,the strategy of combining photoimmunotherapy with other immunotherapies,such as immune checkpoint blockade,chimeric antigen receptor-T cell or cytokine therapy,can greatly enhance the effectiveness of oncology treatment and reduce the traditional adverse effects.Thus,it is very valuable to summarize the research progress in biomaterial-assisted combination photoimmunotherapy for clinical translation.In this review,the recent advances in constructing multifunctional nano-biomaterials for combinatorial photoimmunotherapy of cancer are summarized.Furthermore,the opportunities,challenges,future trends and prospects in this field are also analyzed to pave the way for advancing the next generation of clinical cancer management strategies.
基金supported by the Natural Science Foundation of Shaanxi Province(2023-YBSF-270)the Horizontal Project of the First Affiliated Hospital of Xi’an Jiaotong University(202304174)+1 种基金the Undergraduate Innovation and Entrepreneurship Training Program of Jiangsu Province(202310304155Y)Omer Aras was partially supported by the US National Institutes of Health/National Cancer Institute Cancer Center Support Grant(P30 CA008748).
文摘Sonodynamic therapy(SDT)is an innovative cancer therapy modality that harnesses the energy of ultrasound to activate sonosensitizers for producing reactive oxygen species(ROS),culminating in the eradication of tumor cells.Compared with photodynamic therapy,SDT has the capacity to penetrate deeply into biological tissues,thereby holding significant promise for addressing deeply situated or surgically inaccessible tumors.The effectiveness of SDT is greatly dependent on the characteristics of the sonosensitizers,and unlike inorganic sonosensitizers,organic sonosensitizers offer a more controlled synthesis process and have excellent biocompatibility.This review presents ameticulous undertaking to categorize organic sonosensitizers and elucidate theirmechanisms of action and therapeutic effects in the context of SDT.Design strategies for sonosensitizers are also summarized,and we emphasize the critical role of nanotechnology in tumor localization,imaging,and multimodal synergistic therapy,offering an innovative approach for achieving precise tumor targeting.In addition,the synergistic impact of SDT is delineated when integrated with other oncological modalities,such as photothermal therapy and photodynamic therapy,to enhance therapeutic efficacy.Finally,the review also discusses challenges and future perspectives for the advancement of clinical SDT within the realm of oncology.
基金funded by the National Natural Science Foundation of China(81903662,81860630 and 51903201)China Postdoctoral Science Foundation(2019M661057 and 2019M653660)+2 种基金Natural Science Foundation of Shaanxi Province(2020JQ-086,China)the Natural Science Foundation of Jiangxi(20181BAB205087,China)the Key Project of Jiangxi(20192ACB70012,China)
文摘Proteases have a fundamental role in maintaining physiological homeostasis,but their dysregulation results in severe activity imbalance and pathological conditions,including cancer onset,progression,invasion,and metastasis.This striking importance plus superior biological recognition and catalytic performance of proteases,combining with the excellent physicochemical characteristics of nanomaterials,results in enzyme-activated nano-drug delivery systems(nanoDDS)that perform theranostic functions in highly specific response to the tumor phenotype stimulus.In the tutorial review,the key advances of protease-responsive nanoDDS in the specific diagnosis and targeted treatment for malignancies are emphatically classified according to the effector biomolecule types,on the premise of summarizing the structure and function of each protease.Subsequently,the incomplete matching and recognition between enzyme and substrate,structural design complexity,volume production,and toxicological issues related to the nanocomposites are highlighted to clarify the direction of efforts in nanotheranostics.This will facilitate the promotion of nanotechnology in the management of malignant tumors.
基金National Natural Science Foundation of China,Grant/Award Number:22107087Yong Talent Support Plan of Xi’an Jiaotong University,Grant/Award Number:YX6J024+1 种基金Science and Technology Planning Project of Guangzhou,Grant/Award Number:202002030089Key Projects of Social Welfare and Basic Research of Zhongshan City,Grant/Award Number:2021B2007。
文摘Fluorescent analysis of bone provides valuable insights into bone structures.However,conventional dyes suffer from low specificity on bone tissue,small stokes shift,short fluorescent lifetime,and aggregation-caused quenching effect,which result in low efficacy and artifacts.In this work,we design an aggregation-induced emission(AIE)-active iridium(III)complex(Ir-BP2)as a highly selective,convenient,nondestructiveness,and dual-mode staining agent for bone analysis.Ir-BP2 containing phosphonate groups selectively binds to hydroxyapatites,the main component of bone matrix,and exhibits turn-on AIE phosphorescence with prolonged lifetime.Ir-BP2 exhibits promising biosafety and offers higher accuracy in staining calcium deposits than conventional Alizarin Red S staining assay when it is employed in real-time monitoring of osteogenesis differentiation process.A ready-to-use staining spray of Ir-BP2 is fabricated.By using fluorescent imaging and lifetime imaging,Ir-BP2 staining provides valuable insights into bone microstructure analysis,microdamage diagnosis,and bone growth state identification.Further,Ir-BP2 is successfully applied on a human spine vertebra for diagnosing bone invasiveness of eosinophilic granuloma,validating its clinical practice.This work presents a powerful tool in bone analysis and will lead to new approaches for the diagnosis and treatment of bone-related diseases.
基金supported by the National Key Research and Development Program of China(grant no.2019YFD1000500)the 2020 Research Program of Sanya Yazhou Bay Science and Technology City(grant no.SKJC-2020-02-002)+2 种基金the Central Public-Interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences(grant nos.1630012019009,1630052016005,1630052016006,1630052017021,and 1630052019023)the Central Public-Interest Scientific Institution Basal Research Fund for Innovative Research Team Program of CATAS(grant nos.17CXTD-28 and 1630052017017)the ear-marked fund for Modern Agro-industry Technology Research System(grant no.nycytx-11).
文摘Dear Editor,Generation of heterozygous genomes by hybridization between or within species can help maintain plant diversity and serve as a potential source of new species(Baek et al.,2018).Moreover,genomic heterozygosity is associated with genomic coadaptation,developmental stability,and heterosis.Accurate definition of alleles in haplotypes is necessary to precisely characterize allelic variation controlling agriculturally important traits(Shi et al.,2019).Currently,most released genomes have mosaic assembly of haplotypes due to random selection or collapse of alleles during genome assembly(Shi et al.,2019),which masked allelic variation and functional differentiation of divergent alleles in heterozygous species.
