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β-Cyclodextrin-modified AuBi metallic aerogels enable efficient peroxidase mimicking for colorimetric sensing of urease-positive pathogenic bacteria

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Nano Research 2023年第7期16卷 9663-9671页

作者： Minghui Wang Peixian Wu Sha Yang Gui-long Wu Na Li Xiaofeng Tan Qinglai Yang Center for molecular imaging Probe Hunan Province Key Laboratory of Tumor Cellular and Molecular PathologyCancer Research InstituteHengyang Medical SchoolUniversity of South ChinaHengyang 421001China

The detection of pathogenic bacteria with improved accessibility,reduced analysis time,and increased sensitivity is of great importance for diagnosing the infected *** have attracted rising attention in the bioassay *** a model nanozyme needs the combined merit of sensible nanostructures and a large specific surface area to guarantee exceptional enzyme-mimic ***,aβ-cyclodextrin modified AuBi aerogel is prepared by a one-pot reduction *** introduction ofβ-cyclodextrin(featured with a hydrophobic cavity and hydrophilic surface)enhances the catalytic activity of AuBi aerogels by engendering host-guest complex and improving dispersity/*** on the specific urea hydrolysis,which could produce NH_(3)to raise pH by urease,the pH up-regulation would inhibit the peroxidase-mimicking performances ofβ-cyclodextrin/AuBi ***,the sensitive colorimetric detection platform for urease activity could be ***,the sensing platform can detect straightforwardly urease-positive Proteus mirabilis in urine circumstances with a wide detection range and a low limit of detection(LOD)of 4 colony-forming unit(CFU)·mL^(-1).The reproducibility,stability,and specificity of this approach are verified to be ***,as an inhibitor of urease activity,the fluoride ion could be detected by the constructed sensing platform sensitively and ***,this work provides a blueprint for designing an ideal nanozyme and paves a new roadway for detecting pathogenic bacteria.

关键词： metallic aerogels surface modification urea hydrolysis urease activity fluoride ion proteus mirabilis bacteria detection

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Environmentally responsive dual-targeting nanotheranostics for overcoming cancer multidrug resistance

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Science Bulletin 2019年第10期64卷 705-714页

作者： Caixia Yang Xin Pang Weihai Chen Xiaoyong Wang Gan Lin Chengchao Chu Xianzheng Zhang Xianming Deng Xiaoyuan Chen Gang Liu State Key Laboratory of molecular Vaccinology and molecular Diagnostics and Center for molecular imaging and Translational Medicine School of Public Health Xiamen University Xiamen 361102 China Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry Wuhan University Wuhan 430072 China State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signaling Network School of Life Sciences Xiamen University Xiamen 361102 China Laboratory of molecular imaging and Nanomedicine National Institute of Biomedical Imaging and Bioengineering (NIBIB) National Institutes of Health (NIH) Bethesda MD 20892 USA

The development of multiple drug resistance(MDR) to chemotherapy and subsequent treatment failures are major obstacles in cancer therapy. An attractive option for combating MDR is inhibiting the expression of P-glycoprotein(P-gp) in tumor cells. Here, we report a novel chemosensitizing agent, XMD8-92,which can down-regulate P-gp. To enhance the specificity of MDR chemotherapy, a promising nanotheranostic micelle system based on poly(ethylene glycol)-blocked-poly(L-leucine)(PEG-b-Leu) was developed to simultaneously carry the anticancer drug doxorubicin, chemosensitizing agent XMD8-92, and superparamagnetic iron oxide nanoparticles(SPIOs). Featured with MDR environmentally responsive dual-targeting capability, controllable drug delivery, and efficient magnetic resonance(MR) imaging characteristics, the prepared nanotheranostics(DXS@NPs) showed outstanding in vitro cytotoxicity on MDR cells(SCG 7901/VCR) with only 53% of cells surviving compared to 90% of DOX-treated ***, efficient tumor inhibition and highly reduced systemic toxicity were exhibited by MDR tumor-bearing mice treated with DXS@NPs. Overall, the environmentally responsive dual-targeting nanotheranostics represent a promising approach for overcoming cancer MDR.

关键词： Cancer chemosensitization Multidrug resistance P-glycoprotein pH-responsive Magnetic resonance imaging

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De Novo Design of a Highly Stable Ovoid TIM Barrel:Unlocking Pocket Shape towards Functional Design

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BioDesign Research 2022年第1期2022卷 68-80页

作者： Alexander E.Chu Daniel Fernandez Jingjia Liu Raphael R.Eguchi Po-Ssu Huang Biophysics program Stanford UniversityStanfordCAUSA Department of Bioengineering Stanford UniversityStanfordCAUSA program in Chemistry EngineeringAnd Medicine for Human Health(ChEM-H)Stanford UniversityStanfordCAUSA stanford ChEM-H Macromolecular Structure Knowledge CenterStanford UniversityStanfordCAUSA Department of Biochemistry Stanford UniversityStanfordCAUSA Bio-X Institute Stanford UniversityStanfordCAUSA

The ability to finely control the structure of protein folds is an important prerequisite to functional protein design. The TIM barrelfold is an important target for these efforts as it is highly enriched for diverse functions in nature. Although a TIM barrel proteinhas been designed de novo, the ability to finely alter the curvature of the central beta barrel and the overall architecture of the foldremains elusive, limiting its utility for functional design. Here, we report the de novo design of a TIM barrel with ovoid (twofold)symmetry, drawing inspiration from natural beta and TIM barrels with ovoid curvature. We use an autoregressive backbonesampling strategy to implement our hypothesis for elongated barrel curvature, followed by an iterative enrichment sequencedesign protocol to obtain sequences which yield a high proportion of successfully folding designs. Designed sequences arehighly stable and fold to the designed barrel curvature as determined by a 2.1Å resolution crystal structure. The designs showrobustness to drastic mutations, retaining high melting temperatures even when multiple charged residues are buried in thehydrophobic core or when the hydrophobic core is ablated to alanine. As a scaffold with a greater capacity for hosting diversehydrogen bonding networks and installation of binding pockets or active sites, the ovoid TIM barrel represents a major steptowards the de novo design of functional TIM barrels.

关键词： structure curvature backbone

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Metal-organic frameworks nanoswitch:Toward photo-controllable endo/lysosomal rupture and release for enhanced cancer RNA interference

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Nano Research 2020年第1期13卷 238-245页

作者： Gan Lin Yang Zhang Long Zhang Junqing Wang Ye Tian Wen Cai Shangui Tang Chengchao Chu JiaJing Zhou Peng Mi Xiaoyuan Chen Gang Liu State Key Laboratory of molecular Vaccinology and molecular Diagnostics&Center for molecular imaging and Translational Medicine School of Public HealthXiamen UniversityXiamen361102China The Department of Chemical Engineering The University of MelbourneParkvilleVictoria3010Australia School of Chemical and Biomedical Engineering Nanyang Technological UniversitySingapore637457Singapore State Key Laboratory of Biotherapy and Cancer Center West China HospitalCollaborative Innovation Center for BiotherapySichuan UniversityChengdu610041China Laboratory of molecular imaging and Nanomedicine National Institute of Biomedical Imaging and BioengineeringNational Institutes of HealthBethesdaMD20892USA

Endo/lysosomal escape and gene release are two critical bottlenecks in gene ***,a novel photo-controllable metal-organic frameworks(MOFs)nanoswitch is rationally designed for enhancing small interfering RNA(siRNA)*** single laser triggers the“off-to-on”switching of MOFs nanocomplexes,inducing significant siRNA release accompanied by rapid MOFs dissociation into protonatable 2-methylimidazalo and osmotic rupturing Zn2+ions,which cooperatively contribute to remarkable endo/lysosomal rupture(∼90%).The simultaneous endo/lysosomal rupture and release enable a high spatio-temporal control on RNA interference for effective cancer ***,the“off-to-on”switching also activates fluorescence recovery for real-time monitoring siRNA *** nanoswitch could easily be extended to deliver other therapeutic agents(e.g.,DNA,protein,anticancer drug)for overcoming endo/lysosomal entrapment.

关键词： metal-organic frameworks endo/lysosomal rupture and release photo-controllable nanoswitch RNA interference cancer therapy

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Hollow iron oxide nanoparticles as multidrug resistant drug delivery and imaging vehicles

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Nano Research 2013年第1期6卷 1-9页

作者： Ruijun Xing Ashwinkumar A. Bhirde Shouju Wang Xiaolian Sun Gang Liu Yanglong Hou Xiaoyuan Chen Laboratory of molecular imaging and Nanomedicine (LOMIN) National Institute of Biomedical Imaging and Bioengineering (NIBIB) National Institutes of Health (NIH) Bethesda MD 20892 USA Department of Materials Science and Engineering College of Engineering Peking University Beijing 100871 China Center for molecular imaging and Translational Medicine School of Public Health Xiamen University Xiamen 361005 China

Magnetic nanopartides have been used as drug delivery vehicles against a number of cancer cells. Most of these theranostic formulations have used solid iron oxide nanoparticles （SIONPs） loaded with chemotherapeutics as nano-carrier formulation for both magnetic resonance imaging （MRI） and cancer therapy. In this study, we applied the dopamine-plus-human serum albumin （HSA） method to modify hollow iron oxide nanoparticles （HIONPs） and encapsuated doxorubicin （DOX） within the hollow porous structure of the nano-carrier. The new delivery system can load more drug than solid iron oxide nanoparticles of the same core size using the same coating strategy. The HIONPs-DOX formulation also has a pH-dependent drug release behaviour. Compared with free DOX, the HIONPs-DOX were more effectively uptaken by the multidrug resistant OVCAR8- ADR cells and consequently more potent in killing drug resistant cancer cells. MRI phantom and cell studies also showed that the HIONPs-DOX can decrease the T2 MRI signal intensity and can be used as a MR/contrast agent while acting as a drug delivery vehicle. For the first time, the dual application of chemo drug transport and MR imaging using the HIONPs-DOX formulation was achieved against both DOX-sensitive and DOX-resistant cancer cells.

关键词： drug resistance hollow nanoparticles doxorubicin magnetic resonanceimaging (MRI) drug delivery

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In vivo radiometric analysis of glucose uptake and distribution in mouse bone

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Bone Research 2016年第1期4卷 31-38页

作者： Meredith L Zoch Diane S Abou Thomas L Clemens Daniel LJ Thorek Ryan C Riddle Department of Orthopaedic Surgery Johns Hopkins University School of Medicine Baltimore USA Division of Nuclear Medicine an molecular imaging Department of Radiology and Radiological Science Johns Hopkins University School of Medicine Baltimore USA Baltimore Veterans Administration Medical Center Baltimore USA Department of Oncology Cancer Molecular and Functional Imaging Program Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore USA

Bone formation and remodeling occurs throughout life and requires the sustained activity of osteoblasts and osteoclasts, particularly during periods of rapid bone growth. Despite increasing evidence linking bone cell activity to global energy homeostasis, little is known about the relative energy requirements or substrate utilization of bone cells. In these studies, we measured the uptake and distribution of glucose in the skeleton in vivo using positron-emitting 18F-fluorodeoxyglucose （[lSF]-FDG） and non-invasive, high-resolution positron emission tomography/computed tomography （PE~/CT） imaging and ex vivo autoradiography. Assessment of [~SF]-FDG uptake demonstrated that relative to other tissues bone accumulated a significant fraction of the total dose of the glucose analog..Skeletal accumulation was greatest in young mice undergoing the rapid bone formation that characterizes early development. PET/CT imaging revealed that [lSF]-FDG uptake was greatest in the epiphyseal and metaphyseal regions of long bones, which accords with the increased osteoblast numbers and activity at this skeletal site. Insulin administration significantly increased skeletal accumulation of [lSF]-FDG, while uptake was reduced in mice lacking the insulin receptor specifically in osteoblasts or fed a high-fat diet. Our results indicated that the skeleton is a site of significant glucose uptake and that its consumption by bone cells is subject to regulation by insulin and disturbances in whole-body metabolism.

关键词： bone FDG

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Specific staining and precise killing of cancer cells through fusion of pharmaceutical chemistry and π-bridge effect design philosophy

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Science China Chemistry 2025年

作者： Qiong Liu Qiyun Deng Changxu Zhu Kongqi Chen Lidan Chen Zhaohui Sun Ben Zhong Tang Zhiming Wang AIE Institute Center for Aggregation-Induced Emission State Key Laboratory of Luminescent Materials and Devices Key Laboratory of Luminescence from Molecular Aggregates of Guangdong Province South China University of Technology Department of Laboratory Medicine General Hospital of Southern Theater Command School of Life Sciences The Chinese University of Hong Kong Shenzhen Institute of Aggregate Science and Technology School of Science and Engineering The Chinese University of Hong Kong HKUST-Shenzhen Research Institute

The development of an advanced phototheranostic platform that combines imaging and therapy in a single agent is an appealing yet challenging *** this study,we successfully constructed three novel fluorescent probes by leveraging pharmaceutical chemistry and the design philosophy of theπ-bridge *** a systematic comparative analysis of their fluorescence properties,water solubility,molecular conformation,and electrostatic potential,we revealed the fundamental principles governing the optical behavior and biological selectivity of these ***,the probe TPhIQ-CNTh demonstrated extended fluorescence in the near-infrared region,a significant aggregation-induced emission (AIE) effect,and the ability to distinguish tumor cells from normal ***,it efficiently generated reactive oxygen species (ROS) and specifically labeled lipid droplets,enabling the precise staining and killing of cancer *** study presents a practical strategy for designing precise tumor treatments that integrate efficient imaging-guided photodynamic therapy (PDT) by harnessing the unique properties of AIE materials.

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Application of machine learning method in optical molecular imaging: a review

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Science China(Information Sciences) 2020年第1期63卷 5-20页

作者： Yu AN Hui MENG Yuan GAO Tong TONG Chong ZHANG Kun WANG Jie TIAN CAS Key Laboratory of molecular imaging Beijing Key Laboratory of Molecular ImagingThe State Key Laboratory of Management and Control for Complex SystemsInstitute of Automation Chinese Academy of Sciences Beijing Advanced Innovation Center for Big Data-Based Precision Medicine School of MedicineBeihang University university of Chinese Academy of Sciences

Optical molecular imaging(OMI) is an imaging technology that uses an optical signal, such as near-infrared light, to detect biological tissue in organisms. Because of its specific and sensitive imaging performance, it is applied in both preclinical research and clinical surgery. However, it requires heavy data analysis and a complex mathematical model of tomographic imaging. In recent years, machine learning(ML)-based artificial intelligence has been used in different fields because of its ability to perform powerful data processing. Its analytical capability for processing complex and large data provides a feasible scheme for the requirement of OMI. In this paper, we review ML-based methods applied in different OMI modalities.

关键词： optical molecular imaging machine learning artificial intelligence

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Gold nanoparticles for cancer theranostics:Abrief update

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Journal of Innovative Optical Health Sciences 2016年第4期9卷 1-10页

作者： Ning Zhao Yongxu Pan Zhen Cheng Hongguang Liu College of Life and Health Sciences Northeastern University ShenYangLiaoningP.R.China Department of Radiology and Bio-X program School of Medicine Stanford UniversityStanfordCAUSA

Gold nanoparticles(AuNPs)exhibit superior optical and physical properties for more effective treatment of cancer through incorporating both diagnostic and ther apeutic functions into one single plat *** ability to passively accumulate on tumor cells provides AuNPs the oppor-tunity to become an attractive contrast agent for X-ray based computed tomography(CT)imaging in *** of facile surface modification,various size and shape of AuNPs have been extensively funct ionalized and applied as active nanoprobes and drug carriers for cancer targeted ***,their capabilities on producing photoacoustic(PA)signals and photothermal ffects have been used to image and treat tumor progression,***,we review the developments of AuNPs as cancer diagnostics and chemotherapeutic drug vector,summarizing strategies for tumor targeting and their applications in vritro and in vrivo.

关键词： Gold nanoparticles multimodal imaging phototherapy gene therapy drug delivery

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PET probes beyond ^(18)F-FDG

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The Journal of Biomedical Research 2014年第6期28卷 435-446页

作者： Lei Jiang Yingfeng Tu Hongcheng Shi Zhen Cheng Department of Nuclear Medicine Zhongshan HospitalFudan University molecular imaging program at stanford(MIPS) Department of RadiologyStanford Cancer InstituteBio-X ProgramCanary Center at Stanford for Cancer Early DetectionStanford University

During the past several decades,positron emission tomography（PET） has been one of the rapidly growing areas of medical imaging;particularly,its applications in routine oncological practice have been widely *** present,^18F-fluorodeoxyglucose（^18F-FDG） is the most broadly used PET ***,^18F-FDG also suffers many ***,scientists and clinicians are greatly interested in exploring and developing new PET imaging probes with high affinity and *** this review,we briefly summarize the representative PET probes beyond ^18F-FDG that are available for patients imaging in three major clinical areas（oncology,neurology and cardiology）,and we also discuss the feasibility and trends in developing new PET probes for personalized medicine.

关键词： PET molecular probes personalized medicine

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