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D-type neuropeptide decorated AIEgen/RENP hybrid nanoprobes with light-driven ROS generation ability for NIR-Ⅱ fluorescence imaging-guided through-skull photodynamic therapy of gliomas

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Aggregate 2024年第1期5卷 185-195页

作者： Xuelu He Yuan Luo Yanying Li Yuanbo Pan ryan t.k.kwok Lulu He Xiaolin Duan Pengfei Zhang Aiguo Wu Ben Zhong tang Juan Li Ningbo key Laboratory of Biomedical Imaging Probe Materials and technology Zhejiang International Cooperation Base of Biomedical Materials Technology and ApplicationChinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and DevicesNingbo Cixi Institute of Biomedical EngineeringZhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingboP.R.China Guangdong key Laboratory of Nanomedicine Shenzhen Engineering Laboratory of Nanomedicine and NanoformulationsCAS-HK Joint Lab for BiomaterialsResearch Laboratory for Biomedical Optics and Molecular ImagingShenzhen Key Laboratory for Molecular ImagingCAS Key Lab for Health InformaticsShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenP.R.China Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction and Institute for Advanced StudyThe Hong Kong University of Science and Technology(HKUST)KowloonP.R.China School of Science and Engineering Shenzhen Institute of Aggregate Science and TechnologyThe Chinese University of Hong KongShenzhenP.R.China

Glioma is one of the most common malignant tumors of the central nervous system,leading high mortality rates in ***-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)***,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 *** 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 *** theranostic agent was further decorated with D-type neuropeptide DNPY for crossing BBB and targeting *** 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 *** 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.

关键词： aggregation-induced emission D-type neuropeptide glioma photodynamic therapy rare-earth doping nanoparticles

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Strategies in boosting photosensitization for biomedical applications

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Science China Chemistry 2022年第4期65卷 647-649页

作者： Ming Chen ryan t.k.kwok Youhong tang Dan Ding College of Chemistry and Materials Science Jinan UniversityGuangzhou 510632China Frontiers Science Center for Cell Responses State Key Laboratory of Medicinal Chemical BiologyKey Laboratory of Bioactive MaterialsMinistry of EducationCollege of Life SciencesNankai UniversityTianjin 300071China Department of Nephrology Huai’an Hospital Affiliated to Xuzhou Medical College and Huai’an Second HospitalHuai’an 223002China Department of Chemistry The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and ReconstructionInstitute for Advanced StudyDepartment of Chemical and Biological EngineeringThe Hong Kong University of Science and TechnologyHong KongChina Australia-China Joint Centre for Personal Health technologies Medical Device Research InstituteCollege of Science and EngineeringFlinders UniversitySouth Australia 5042Australia Guangdong Provincial key Laboratory of Luminescence from Molecular Aggregates South China University of TechnologyGuangzhou 510640China

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... 详细信息

关键词： treatment boosting immunotherapy

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Enzyme-free photothermally amplified fluorescent immunosorbent assay(PAFISA)for sensitive cytokine quantification

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Aggregate 2023年第6期4卷 137-145页

作者： Dian Li Wei He Xuyan Lin Xiaodong Cui Stefan Nagl Angela Ruohao Wu ryan t.k.kwok Renhua Wu Ben Zhong tang Department of Medical Imaging The 2nd Affiliated HospitalMedical CollegeShantou UniversityShantouP.R.China Department of Physics Shantou UniversityShantouP.R.China Department of Physics University of Hong KongHong Kong SARP.R.China Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and ReconstructionThe Hong Kong University of Science and TechnologyKowloonP.R.China Division of Life Science The Hong Kong University of Science and TechnologyKowloonP.R.China HkUSt Fok Ying tung Research Institute GuangzhouP.R.China Department of Chemistry The Hong Kong University of Science and TechnologyKowloonP.R.China Department of Chemical and Biological Engineering The Hong Kong University of Science and TechnologyKowloonP.R.China School of Science and Engineering Shenzhen Key Laboratory of Functional Aggregate MaterialsThe Chinese University of Hong KongShenzhenP.R.China

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 ***-linked immunosorbent assay(ELISA)is one of the most popular methods in cytokine detection,ascribing to the lavish signal amplification methods in the ELISA *** 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 *** to the accumulative effect of heat,photothermal reagents are promising materials in the signal amplification of ***,the lack of efficient photothermal generation material at an aggregate scale may delay the further development of this *** 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 *** photothermal nanoparticles with highly efficient photothermal conversion by harvesting energy via excited-state intramolecular motions and enlarging molar absorptivity were successfully *** 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 *** microscopic imaging integrated with plane sweeping technology provided high spatial resolution and precision,indicating the potential of achieving high throughput profiling at the ***,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.

关键词： cytokine quantitation enzyme free fluorescence intensity ratio metric interleukin-2 microchip microscopic mapping photothermally amplified fluorescent immunosorbent assay

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Aptamer-Anchored Rubrene-Loaded Organic Nanoprobes for Cancer Cell targeting and Imaging

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CCS Chemistry 2019年第3期1卷 251-260页

作者： Yuanyuan Li Chuansheng Li tao Jiang Lihua Zhou Pengfei Zhang ryan t.k.kwok Jacky Wing Yip Lam Ping Gong Lintao Cai Ben Zhong tang Department of Chemistry The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and ReconstructionInstitute for Advanced StudyDepartment of Chemical and Biological EngineeringThe Hong Kong University of Science and TechnologyClear Water BayKowloonChina HkUSt Shenzhen Research Institute Shenzhen 518057China Guangdong key Laboratory of Nanomedicine CAS Key Laboratory of Health InformaticsShenzhen Bioactive Materials Engineering Lab for MedicineInstitute of Biomedicine and Biotechnology.Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Department of Pharmaceutical Sciences Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Dongguan key Laboratory of Drug Design and Formulation technology Key Laboratory for NanomedicineGuangdong Medical UniversityDongguan 523808China Center for Aggregation-Induced Emission NSFC Center for Luminescence from Molecular AggregatesSCUT-HKUST Joint Research LaboratoryState Key Laboratory of Luminescent Materials and DevicesSouth China University of TechnologyGuangzhou 510640China

Fluorescence imaging has become an indispensable technique in cancer research because it can reveal informative molecular,cellular,anatomical,and func-tional *** of advanced fluores-cent probes with superior sensitivity and biological selectivity for fluorescence imaging is thus *** move forward in this direction,we developed an easy self-assembly method for fabricating apta-mer-anchored rubrene-loaded organic fluorescent *** 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 *** 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.

关键词： aptamer organic nanoprobes fluores-cence cancer imaging biomedicine

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taming Reactive Oxygen Species:Mitochondria-targeting Aggregation-Induced Emission Luminogen for Neuron Protection via Photosensitization-triggered Autophagy

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CCS Chemistry 2022年第7期4卷 2249-2257页

作者： Chao Chen Ruoyao Zhang Jianyu Zhang Yufan Zhang Haoke Zhang Zaiyu Wang Xiaolin Huang Sijie Chen ryan t.k.kwok Jacky W.Y.Lam Dan Ding Ben Zhong tang Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and ReconstructionInstitute for Advanced StudyState Key Laboratory of Molecular NanoscienceDivision of Life ScienceDepartment of Chemical and Biological EngineeringThe Hong Kong University of Science and TechnologyClear Water BayKowloonHong Kong 999077 State key Laboratory ofMedicinal Chemical Biology Key Laboratory of Bioactive MaterialsMinistry of EducationCollege of Life SciencesNankai UniversityTianjin 300071 Ming Wai Lau Centre for Reparative Medicine Karolinska InstitutetHong Kong 999077 Center for Aggregation-Induced Emission SCUT-HKUST Joint Research InstituteState Key Laboratory of Luminescent Materials and DevicesSouth China University of TechnologyGuangzhou 510640 Shenzhen Institute of Aggregate Science and technology School of Science and EngineeringThe Chinese University of Hong KongShenzhen 518172 AIE Institute Guangzhou Development DistrictHuangpuGuangzhou 510530

Oxidative damage to cells leads to accumulated harmful wastes,which in turn aggravate the imbalance of reactive oxygen species(ROS)and related ***,provoking the cellular defense system against severe oxidation and maintaining ROS homeostasis are ***,we designed and synthesized a powerful mitochondria-targeting aggregation-induced emission photosensitizer(named DtCSPY)by maximal restriction of heat *** 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 *** 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.

关键词： aggregation-induced emission mitochondrial targeting photosensitizer reactive oxygen species neuron protection

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A versatile AIE fluorogen with selective reactivity to primary amines for monitoring amination,protein labeling,and mitochondrial staining

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聚集体(英文) 2023年第1期4卷 250-259页

作者： Xinyuan He Huilin Xie Lianrui Hu Pengchao Liu Changhuo Xu Wei He Wutong Du Siwei Zhang Hao Xing Xinyue Liu Hojeong Park tsz Shing Cheung Min-Hui Li ryan t.k.kwok Jacky W.Y.Lam Jian Lu Ben Zhong tang Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and ReconstructionState Key Laboratory of Molecular NeuroscienceDivision of Life Science and Department of Chemical and Biological EngineeringThe Hong Kong University of Science and TechnologyKowloonHong KongChina Department of Mechanical Engineering City University of Hong KongGreater Bay Joint DivisionShenyang National Laboratory for Materials ScienceKowloonHong KongChina Chimie Paristech PSL University Paris CNRSInstitut de Recherche de Chimie ParisParisFrance Department of Chemistry Guangdong-Hongkong-Macou Joint Laboratory of Optoelectronic and Magnetic Functional MaterialsThe Hong Kong University of Science and TechnologyKowloonHong KongChina Center for Aggregation-Induced Emission SCUT-HKUST Joint Research InstituteState Key Laboratory of Luminescent Materials and DevicesSouth China University of TechnologyGuangzhouChina School of Science and Engineering Shenzhen Key Laboratory of Functional Aggregate MaterialsThe Chinese University of Hong KongShenzhen CityGuangdongChina

Specific bioconjugation for native primary amines is highly valuable for both chemistry and biomedical *** 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 ***,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 *** is AIE-active and capable of solid-state ***,its electrospun films are manufactured for visualization of amine diffusion and leakage *** also shows good biocompatibility and potential mitochondria-staining ability,which provides new insight for organelle-staining probe *** 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.

关键词： aggregation-induced emission(AIE) bioconjugation mitochondria-staining primary amines protein labeling

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AIE Featured Inorganic-Organic Core@Shell Nanocomplex for Highly efficient SiRNA Delivery and Real-time Monitoring

AIE Featured Inorganic-Organic Core@Shell Nanocomplex for Hi...

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中国化学会第十三届全国分析化学年会

作者： Xuewen He Feng Yin Ling-Hong Xiong Zheng Zhao ryan t.k.kwok Jacky W.Y.Lam Ben Zhong tang Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Centre for Tissue Restoration and Reconstruction Institute for Advanced Study Division of Life Science and Division of Biomedical Engineering The Hong Kong University of Science and Technology

RNA interference（RNAi） is emerging as one of the most powerful technologies for sequence-specific suppression of genes and presents a great potential in biomedical applications ranging from gene analysis to diseases therapeutics. Considering the drawbacks of current si RNA delivery vehicles in biocompatibility and efficacy, the development of high efficient si RNA delivery nanocarrier associated with self-monitoring functionality is of great significance. Herein, by taking advantage of aggregation-induced emission luminogens（AIEgens）, a new generation of inorganic/organic core@shell nanocarrier that allowed efficient delivery and real-time monitoring of siRNA in living cells had been developed. the amine groups in the nanocarriers behaved as a proton-absorber and promoted the release of si RNA from endosome. the AIE properties provided a unique fluorescence imaging modality for long-term tracking and intracellular localization of si RNA during transfection. Comparing to the commercial si RNA transfection reagents, the present system displayed a pretty higher efficiency and reproducibility in terms of intracellular transfection and target down regulation with a much lower cytotoxicity.

关键词： aggregation-induced emission(AIE) nanocarrier siRNA real-time apoptosis

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A Simple Approach to Bioconjugation at Diverse Levels: Metal-Free Click Reactions of Activated Alkynes with Native Groups of Biotargets without Prefunctionalization

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Research 2018年第1期2018卷 172-183页

作者： Xianglong Hu Xueqian Zhao Benzhao He Zheng Zhao Zheng Zheng Pengfei Zhang Xiujuan Shi ryan t.k.kwok Jacky W.Y.Lam Anjun Qin Ben Zhong tang Department of Chemistry Hong Kong Branch of Chinese National EngineeringResearch Center for Tissue Restoration and ReconstructionInstitute of Advanced StudyState Key Laboratory of Molecular NanoscienceDivision of Life Science and Diversion of Biomedical EngineeringTe Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Ministry of Education key Laboratory of Laser Life Science&Institute of Laser Life Science College of BiophotonicsSouth China Normal UniversityGuangzhou 510631China HkUSt-Shenzhen Research Institute Shenzhen 518057China NSFC Center for Luminescence from Molecular Aggregates SCUT-HKUST Joint Research InstituteState Key Laboratory of Luminescent Materials and DevicesSouth China University of TechnologyGuangzhou 510640China

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 ***,we provide a strategy for metal-free click bioconjugation at diverse levels based on activated *** 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 *** 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,***,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.

关键词： proof catalysis biomaterials

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the Impact of a Prior Norwood Procedure on Cardiac transplantation in Failed Fontan Physiology

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Congenital Heart Disease 2024年第3期19卷 257-266页

作者： ryan G.McQueen Nikki M.Singh Ronald k.Woods Medical College of Wisconsin Herma Heart Institute at Children’s WisconsinMilwaukeeUSA Division of Pediatric Cardiology Medical College of WisconsinHerma Heart Institute at Children’s WisconsinMilwaukeeUSA Division of Pediatric Cardiothoracic Surgery Medical College of WisconsinHerma Heart Institute at Children’s WisconsinMilwaukeeUSA

Objective:the objective of this study was to compare cardiac transplant operative and postoperative courses of patients with failed Fontan physiology who were initially palliated with a Norwood(FFN)to those without a prior Norwood(FF).Methods:A single-institution retrospective review of all patients with Fontan failure who under-went cardiac transplantation from 2003–2021 was completed-22 underwent prior Norwood(FFN)and 11 did not(FF).Descriptive and inferential statistics were calculated for operative course and patient ***:the operative course of the FFN cohort appeared to be more complex(not statistically significant,but clinically relevant)-this group exclusively experienced sternal re-entry events(3 of 22 patients)and concomitant neo-aor-tic reconstruction(6 patients),had a longer duration of surgery(median of 682 min vs.575.5 min),more time on circulatory arrest(median of 25.5 min vs.12.5 min),and more frequent use of open sternal management[50%of patients(11/22)vs.27.3%of patients(3/11)].Postoperatively,these patients underwent more mediastinal explora-tions[other than sternal closure;40.9%of patients(9/22)vs.18.2%of patients(2/11)],spent more time on mechanical ventilation(median of 5 days vs.2 days),had a longer length of stay(median of 30 days vs.19 days),and required more catheter-based re-interventions[22.7%of patients(5/22)vs.9.1%of patients(1/11)].Conclu-sion:Although underpowered,our results suggest that the operative course of FFN patients is more challenging,based mostly on neo-aortic arch *** turn,this likely leads to a more complex postoperative *** are currently collaborating with other institutions to increase the cohort size and power of the study.

关键词： Fontan Fontan failure Norwood cardiac transplantation

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the secondary injury cascade after spinal cord injury: an analysis of local cytokine/chemokine regulation

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Neural Regeneration Research 2024年第6期19卷 1308-1317页

作者： Daniel J.Hellenbrand Charles M.Quinn Zachariah J.Piper ryan t.Elder Raveena R.Mishra taylor L.Marti Phoebe M.Omuro Rylie M.Roddick Jae Sung Lee William L.Murphy Amgad S.Hanna Department of Neurosurgery University of Wisconsin-Madison School of Medicine and Public Health Department of Biomedical Engineering University of Wisconsin-Madison Department of Orthopedics and Rehabilitation University of Wisconsin-Madison Department of Materials Science and Engineering University of Wisconsin-Madison Forward BIO Institute University of Wisconsin-Madison

After spinal cord injury, there is an extensive infiltration of immune cells, which exacerbates the injury and leads to further neural degeneration. therefore, a major aim of current research involves targeting the immune response as a treatment for spinal cord injury. Although much research has been performed analyzing the complex inflammatory process following spinal cord injury, there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation. the objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury, identify sexual dimorphisms in terms of cytokine levels, and determine local cytokines that significantly change based on the severity of spinal cord injury. Rats were inflicted with either a mild contusion, moderate contusion, severe contusion, or complete transection, 7 mm of spinal cord centered on the injury was harvested at varying times post-injury, and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay. Results demonstrated pro-inflammatory cytokines including tumor necrosis factor α, interleukin-1β, and interleukin-6 were all upregulated after spinal cord injury, but returned to uninjured levels within approximately 24 hours post-injury, while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury. In contrast, several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury. After spinal cord injury, tissue inhibitor of metalloproteinase-1, which specifically affects astrocytes involved in glial scar development, increased more than all other cytokines tested, reaching 26.9-fold higher than uninjured rats. After a mild injury, 11 cytokines demonstrated sexual dimorphisms; however, after a severe contusion only leptin levels were different between female and male rats. In conclus

关键词： astrocytes chemokines cytokines inflammation macrophages microglia secondary damage spinal cord injury

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