Glioma is one of the most common malignant tumors of the central nervous system,leading high mortality rates in human.Aggregation-induced emission(AIE)photosensitizers-based photodynamic therapy(PDT)has emerged as a p...Glioma is one of the most common malignant tumors of the central nervous system,leading high mortality rates in human.Aggregation-induced emission(AIE)photosensitizers-based photodynamic therapy(PDT)has emerged as a promising therapeutic strategy for least-invasive treatment of glioma,which involves local irradiation of the tumor using an external near-infrared(NIR)laser.Unfortunately,most AIE photosensitizers suffered from poorly penetration of the visible light excitation,bad spatiotemporal resolution in deep tissues and low efficient blood-brain barrier(BBB)crossing ability,which greatly limited the clinical practice of AIE photosensitizers for especially deep-seated brain tumor treatment.In this work,we developed a multifunctional NIR-driven theranostic agent through hybrid of AIE photosensitizers TIND with rare-earth doping nanoparticles(RENPs)NaGdF4:Nd/Yb/Tm with up/down dual-mode conversion luminescence.The theranostic agent was further decorated with D-type neuropeptide DNPY for crossing BBB and targeting glioma.Under the 808-nm light irradiation,the down-conversion NIR-II luminescence could indicate the position glioma and the upconversion NIR-I luminescence could trigger the AIE photosensitizers producing reactive oxygen species to inhibit orthotopic glioma tumor growth in situ.These results demonstrate that the integration of Dtype neuropeptide,AIE photosensitizers and RENPs could be promising candidates for in vivo NIR-II fluorescence image-guided through-skull PDT treatments of brain tumors.展开更多
Cytokine monitoring has attracted great attention due to its significance in the diagnosis and treatment of many diseases,such as tumors,microbial infections,and immunological diseases.Enzyme-linked immunosorbent assa...Cytokine monitoring has attracted great attention due to its significance in the diagnosis and treatment of many diseases,such as tumors,microbial infections,and immunological diseases.Enzyme-linked immunosorbent assay(ELISA)is one of the most popular methods in cytokine detection,ascribing to the lavish signal amplification methods in the ELISA platform.In addition to classical enzymes,other signal amplifiers such as fluorescent probes,artificial nano-enzymes,and photothermal reagents have been applied to reduce the detection limit and produce more sensitive ELISA kits.Due to the accumulative effect of heat,photothermal reagents are promising materials in the signal amplification of ELISA.However,the lack of efficient photothermal generation material at an aggregate scale may delay the further development of this area.In this contribution,based on an efficient organic photothermal aggregate material,an enzyme-free photothermally amplified fluorescent immunosorbent assay system consisting of an assay microfluidic chip and detecting platform was developed.The photothermal nanoparticles with highly efficient photothermal conversion by harvesting energy via excited-state intramolecular motions and enlarging molar absorptivity were successfully prepared.The detection concentration at 50 pg/mL of interleukin-2 was achieved,realizing a signal improvement of detection limits by 20-fold compared to that of previously reported photothermal ELISA.The microscopic imaging integrated with plane sweeping technology provided high spatial resolution and precision,indicating the potential of achieving high throughput profiling at the microscale.Moreover,as an alternative excitation source,light-emitting diode not only provided a more affordable and miniaturized detection system but also revealed the great feasibility of intramolecular motion-induced photothermy nanoparticles for biological analyses.展开更多
Specific bioconjugation for native primary amines is highly valuable for both chemistry and biomedical research.Despite all the efforts,scientists lack a proper strategy to achieve high selectivity for primary amines,...Specific bioconjugation for native primary amines is highly valuable for both chemistry and biomedical research.Despite all the efforts,scientists lack a proper strategy to achieve high selectivity for primary amines,not to mention the requirement of fast response in real applications.Herein,we report a chromone-based aggregation-induced emission(AIE)fluorogen called CMVMN as a self-reporting bioconjugation reagent for selective primary amine identification,and its applications for monitoring bioprocesses of amination and protein labeling.CMVMN is AIE-active and capable of solid-state sensing.Thus,its electrospun films are manufactured for visualization of amine diffusion and leakage process.CMVMN also shows good biocompatibility and potential mitochondria-staining ability,which provides new insight for organelle-staining probe design.Combined with its facile synthesis and good reversibility,CMVMN would not only show wide potential applications in biology,but also offer new possibilities for molecular engineering.展开更多
Te efcient bioconjugation of functional groups/molecules to targeted matrix and bio-related species drives the great development of material science and biomedicine,while the dilemma of metal catalysis,uneasy premodif...Te efcient bioconjugation of functional groups/molecules to targeted matrix and bio-related species drives the great development of material science and biomedicine,while the dilemma of metal catalysis,uneasy premodifcation,and limited reaction efciency in traditional bioconjugation has restricted the booming development to some extent.Here,we provide a strategy for metal-free click bioconjugation at diverse levels based on activated alkynes.As a proof-of-concept,the abundant native groups including amine,thiol,and hydroxyl groups can directly react with activated alkynes without any modifcation in the absence of metal catalysis.Trough this strategy,high-efcient modifcation and potential functionalization can be achieved for natural polysaccharide,biocompatible polyethylene glycol(PEG),synthetic polymers,cell penetrating peptide,protein,fast whole-cell mapping,and even quick diferentiation and staining of Gram-positive bacteria,etc.Terefore,current metal-free click bioconjugation strategy based on activated alkynes is promising for the development of quick fuorescence labeling and functional modifcation of many targets and can be widely applied towards the fabrication of complex biomaterials and future in vivo labeling and detection.展开更多
Photodynamic therapy(PDT)has emerged as an effective treatment method for its few adverse effects,little invasiveness,short treatment time and low cost[1,2].The rapid development of PDT has dramatically boosted its mu...Photodynamic therapy(PDT)has emerged as an effective treatment method for its few adverse effects,little invasiveness,short treatment time and low cost[1,2].The rapid development of PDT has dramatically boosted its multifaceted applications in cancer treatment,antibacterial and immunotherapy,etc.[3-5].展开更多
Oxidative damage to cells leads to accumulated harmful wastes,which in turn aggravate the imbalance of reactive oxygen species(ROS)and related diseases.Therefore,provoking the cellular defense system against severe ox...Oxidative damage to cells leads to accumulated harmful wastes,which in turn aggravate the imbalance of reactive oxygen species(ROS)and related diseases.Therefore,provoking the cellular defense system against severe oxidation and maintaining ROS homeostasis are desired.Herein,we designed and synthesized a powerful mitochondria-targeting aggregation-induced emission photosensitizer(named DTCSPY)by maximal restriction of heat dissipation.It is demonstrated that taming ROS generation within mitochondria through photosensitization-triggered autophagy via DTCSPY achieved a better neuroprotective effect against oxidative damages than Nacety-L-cysteine and vitamin C.This work not only provides a new way to design high-performance photosensitizers by regulating the photophysical property,but also verifies the concept that taming ROS can be used for cell protection against destructive oxidation,thereby displaying broad prospects for alleviating oxidation-related diseases and promoting cell-based therapy.展开更多
Fluorescence imaging has become an indispensable technique in cancer research because it can reveal informative molecular,cellular,anatomical,and func-tional insights.Development of advanced fluores-cent probes with s...Fluorescence imaging has become an indispensable technique in cancer research because it can reveal informative molecular,cellular,anatomical,and func-tional insights.Development of advanced fluores-cent probes with superior sensitivity and biological selectivity for fluorescence imaging is thus impera-tive.To move forward in this direction,we developed an easy self-assembly method for fabricating apta-mer-anchored rubrene-loaded organic fluorescent nanoprobes.The aptamer-modified organic nanop-robes integrated the best features of the organic light-emitting materials and the aptamers,thus endowing them with excellent cell-targeting capabil-ity,high stability,and good biocompatibility.By using this general method,a variety of biocompatible and highly bright organic fluorescent nanoprobes based on novel organic light-emitting materials with specific recognition could be easily constructed for real-time biosensing and long-term biomedical imaging.展开更多
基金Natural Science Foundation of China,Grant/Award Numbers:T2222021,32011530115,32025021National Key R&D Programs,Grant/Award Number:2019YFE0198700+2 种基金Science and Technology Bureau of Ningbo City,Grant/Award Numbers:2020Z094,2021Z072Excellent Member of Youth Innovation Promotion Association Foundation of CAS,Grant/Award Number:Y2021079Innovation and Technology Commission,Grant/Award Number:MHP/047/19。
文摘Glioma is one of the most common malignant tumors of the central nervous system,leading high mortality rates in human.Aggregation-induced emission(AIE)photosensitizers-based photodynamic therapy(PDT)has emerged as a promising therapeutic strategy for least-invasive treatment of glioma,which involves local irradiation of the tumor using an external near-infrared(NIR)laser.Unfortunately,most AIE photosensitizers suffered from poorly penetration of the visible light excitation,bad spatiotemporal resolution in deep tissues and low efficient blood-brain barrier(BBB)crossing ability,which greatly limited the clinical practice of AIE photosensitizers for especially deep-seated brain tumor treatment.In this work,we developed a multifunctional NIR-driven theranostic agent through hybrid of AIE photosensitizers TIND with rare-earth doping nanoparticles(RENPs)NaGdF4:Nd/Yb/Tm with up/down dual-mode conversion luminescence.The theranostic agent was further decorated with D-type neuropeptide DNPY for crossing BBB and targeting glioma.Under the 808-nm light irradiation,the down-conversion NIR-II luminescence could indicate the position glioma and the upconversion NIR-I luminescence could trigger the AIE photosensitizers producing reactive oxygen species to inhibit orthotopic glioma tumor growth in situ.These results demonstrate that the integration of Dtype neuropeptide,AIE photosensitizers and RENPs could be promising candidates for in vivo NIR-II fluorescence image-guided through-skull PDT treatments of brain tumors.
基金Basic and Applied Basic Research Foundation of Guangdong Province,Grant/Award Number:2023A1515010702National Natural Science Foundation of China,Grant/Award Numbers:31870981,82020108016+2 种基金Innovation and Technology Commission,Grant/Award Number:ITC-CNERC14SC01Research Grants Council,University Grants Committee,Grant/Award Numbers:16306620,GRF 16209820STU Scientific Research Initiation Grant,Grant/Award Number:NTF22023。
文摘Cytokine monitoring has attracted great attention due to its significance in the diagnosis and treatment of many diseases,such as tumors,microbial infections,and immunological diseases.Enzyme-linked immunosorbent assay(ELISA)is one of the most popular methods in cytokine detection,ascribing to the lavish signal amplification methods in the ELISA platform.In addition to classical enzymes,other signal amplifiers such as fluorescent probes,artificial nano-enzymes,and photothermal reagents have been applied to reduce the detection limit and produce more sensitive ELISA kits.Due to the accumulative effect of heat,photothermal reagents are promising materials in the signal amplification of ELISA.However,the lack of efficient photothermal generation material at an aggregate scale may delay the further development of this area.In this contribution,based on an efficient organic photothermal aggregate material,an enzyme-free photothermally amplified fluorescent immunosorbent assay system consisting of an assay microfluidic chip and detecting platform was developed.The photothermal nanoparticles with highly efficient photothermal conversion by harvesting energy via excited-state intramolecular motions and enlarging molar absorptivity were successfully prepared.The detection concentration at 50 pg/mL of interleukin-2 was achieved,realizing a signal improvement of detection limits by 20-fold compared to that of previously reported photothermal ELISA.The microscopic imaging integrated with plane sweeping technology provided high spatial resolution and precision,indicating the potential of achieving high throughput profiling at the microscale.Moreover,as an alternative excitation source,light-emitting diode not only provided a more affordable and miniaturized detection system but also revealed the great feasibility of intramolecular motion-induced photothermy nanoparticles for biological analyses.
基金National Natural Science Foundation of China,Grant/Award Number:21788102Research Grants Council of Hong Kong,Grant/Award Numbers:16307020,16306620,16305518,N_HKUST609/19,C6009-17G,C6014-20w+1 种基金Innovation and Technology Commission,Grant/Award Numbers:ITC-CNERC14SC01,ITCPD/17-9Natural Science Foundation of Guangdong Province,Grant/Award Number:201913121205002。
文摘Specific bioconjugation for native primary amines is highly valuable for both chemistry and biomedical research.Despite all the efforts,scientists lack a proper strategy to achieve high selectivity for primary amines,not to mention the requirement of fast response in real applications.Herein,we report a chromone-based aggregation-induced emission(AIE)fluorogen called CMVMN as a self-reporting bioconjugation reagent for selective primary amine identification,and its applications for monitoring bioprocesses of amination and protein labeling.CMVMN is AIE-active and capable of solid-state sensing.Thus,its electrospun films are manufactured for visualization of amine diffusion and leakage process.CMVMN also shows good biocompatibility and potential mitochondria-staining ability,which provides new insight for organelle-staining probe design.Combined with its facile synthesis and good reversibility,CMVMN would not only show wide potential applications in biology,but also offer new possibilities for molecular engineering.
基金Tis work was partially supported by the National Science Foundation of China(21788102,21674040)the Innovation and Technology Commission(ITC-CNERC14SC01)+3 种基金the Research Grants Council of Hong Kong(16308016,C6009-17G,N-HKUST604/14,and A-HKUST605/16)the Science and Technology Plan of Shenzhen(JCYJ20170818113538482 and JCYJ20170818113530705)and the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province(2016A030306013)We also acknowledge the support of Hong Kong Scholars Program(XJ2016008)to Xianglong Hu.
文摘Te efcient bioconjugation of functional groups/molecules to targeted matrix and bio-related species drives the great development of material science and biomedicine,while the dilemma of metal catalysis,uneasy premodifcation,and limited reaction efciency in traditional bioconjugation has restricted the booming development to some extent.Here,we provide a strategy for metal-free click bioconjugation at diverse levels based on activated alkynes.As a proof-of-concept,the abundant native groups including amine,thiol,and hydroxyl groups can directly react with activated alkynes without any modifcation in the absence of metal catalysis.Trough this strategy,high-efcient modifcation and potential functionalization can be achieved for natural polysaccharide,biocompatible polyethylene glycol(PEG),synthetic polymers,cell penetrating peptide,protein,fast whole-cell mapping,and even quick diferentiation and staining of Gram-positive bacteria,etc.Terefore,current metal-free click bioconjugation strategy based on activated alkynes is promising for the development of quick fuorescence labeling and functional modifcation of many targets and can be widely applied towards the fabrication of complex biomaterials and future in vivo labeling and detection.
基金supported by the National Key R&D Program of China(Intergovernmental Cooperation Project,2017YFE0132200)the National Natural Science Foundation of China(51961160730,51873092,81921004,2190513)+3 种基金the Fundamental Research Funds for the Central Universities,the Tianjin Science Fund for Distinguished Young Scholars(19JCJQJC61200)the Natural Science Foundation of Guangdong Province(2020A1515010622)the Project of Science and Technology of Guangzhou(202102020308)the Open Fund of Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates(2019B030301003)。
文摘Photodynamic therapy(PDT)has emerged as an effective treatment method for its few adverse effects,little invasiveness,short treatment time and low cost[1,2].The rapid development of PDT has dramatically boosted its multifaceted applications in cancer treatment,antibacterial and immunotherapy,etc.[3-5].
基金financially supported by the National Science Foundation of China(nos.21788102,51873092,and 51961160730)the Research Grants Council of Hong Kong(nos.16305518,16305618,N-HKUST609/19,AHKUST605/16,and C6009-17G)+2 种基金the Innovation and Technology Commission(nos.ITC-CNERC14SC01 and ITCPD/17-9)Ming Wai Lau Centre for Reparative Medicine Associate Member Program(no.MWLC19SC02)the National Key Research and Development Program of China(no.2017YFE0132200).
文摘Oxidative damage to cells leads to accumulated harmful wastes,which in turn aggravate the imbalance of reactive oxygen species(ROS)and related diseases.Therefore,provoking the cellular defense system against severe oxidation and maintaining ROS homeostasis are desired.Herein,we designed and synthesized a powerful mitochondria-targeting aggregation-induced emission photosensitizer(named DTCSPY)by maximal restriction of heat dissipation.It is demonstrated that taming ROS generation within mitochondria through photosensitization-triggered autophagy via DTCSPY achieved a better neuroprotective effect against oxidative damages than Nacety-L-cysteine and vitamin C.This work not only provides a new way to design high-performance photosensitizers by regulating the photophysical property,but also verifies the concept that taming ROS can be used for cell protection against destructive oxidation,thereby displaying broad prospects for alleviating oxidation-related diseases and promoting cell-based therapy.
基金This work was partially supported by the University Grants Committee of Hong Kong(AoE/P-03/08)the Research Grants Council of Hong Kong(16301614,16305015,and N_HKUST604/14)the Innovation and Technology Commission(ITC-CNERC14SC01,ITS/254117,and RE:ITCPD/17-9)。
文摘Fluorescence imaging has become an indispensable technique in cancer research because it can reveal informative molecular,cellular,anatomical,and func-tional insights.Development of advanced fluores-cent probes with superior sensitivity and biological selectivity for fluorescence imaging is thus impera-tive.To move forward in this direction,we developed an easy self-assembly method for fabricating apta-mer-anchored rubrene-loaded organic fluorescent nanoprobes.The aptamer-modified organic nanop-robes integrated the best features of the organic light-emitting materials and the aptamers,thus endowing them with excellent cell-targeting capabil-ity,high stability,and good biocompatibility.By using this general method,a variety of biocompatible and highly bright organic fluorescent nanoprobes based on novel organic light-emitting materials with specific recognition could be easily constructed for real-time biosensing and long-term biomedical imaging.