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Organic Nanocrystals Based on a Solid-emission-tunable AIEgen for Cell Imaging

Chemical Research in Chinese Universities 2021年第1期37卷 129-136页

作者： YANG Liming GUO Lixin YU Hao WANG Guan SUN Jiangman ZHANG Pengfei GU Xinggui TANG Ben Zhong Beijing Advanced Innovation Center for Soft Matter Science and Engineering College of Materials Science and EngineeringState Key Laboratory of Chemical Resource EngineeringBeijing University of Chemical TechnologyBeijing100029P.R.China Guangdong Key laboratory of nanomedicine Shenzhen Engineering Laboratory of Nanomedicine and NanoformulationsCAS Key Laboratory of Health InformaticsInstitute of Biomedicine and BiotechnologyShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen518055P.R.China Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and ReconstructionInstitute for Advanced StudyThe Hong Kong University of Science and TechnologyHong KongP.R.China

The development of fluorescent nanocrystals based on organic small molecules is of great importance in bioimaging due to the merits of easy modification,high brightness and excellent photostability,however suffering from the emission-detrimental aggregation-caused quenching(ACQ)***,we successfully designed and synthesized an AIE-active di(N,N-dimethylaniline)-dibenzofulvene(named as NFTPE),which exhibits the crystallization-induced emission enhancement(CIEE)***,two types of yellow-and orange-emissive crystals for NFTPE were obtained,exhibiting aggregation microenvironment-dependent emission tuning in the solid ***-crystal analysis and density functional theory(DFT)calculations reveal that different aggregation microenvironments result in the distinct molecular conformation for various ***,the crystallization of NFTPE in an aqueous solution under the assistance of amphiphilic PEG polymer matrices could be monitored in situ by the fluorescence changes,facilitating the preparation of NFTPE nanocrystals(NFTPE-NCs)by adjusting the aggregation *** obtained NFTPE-NCs exhibit the superior performance in cell imaging in respect to high brightness,photostability,and biocompatibility,thus demonstrating the potential in bioimaging applications.

关键词： Aggregation-induced emission(AIE) Crystallization-induced emission enhancement(CIEE) Aggregation microenvironment Nanocrystal Cell imaging

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Discovery of Novel Long-Chain Alkenyl Diacid Derivatives as ACLY Inhibitors

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Chinese Journal of Chemistry 2022年第22期40卷 2663-2670页

作者： Gao-Lei Song Lei Cao Mei Zhang Yu-Rou Yang Jie Ma Zhi-Fu Xie Jing-Ya Li Fa-Jun Nan State Key laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences No.19A Yuquan RoadBeijing 100049China Yantai Key laboratory of nanomedicine&Advanced Preparations Yantai Institute of Materia MedicaYantaiShandong 264000China

ATP citrate lyase(ACLY)synthesizes cytosolic acetyl coenzyme A(acetyl-CoA),an essential biosynthetic precursor for lipid synthesis and the acetyl donor required for protein *** aberrant expression and activity of ACLY has been documented in multiple human ***-1002 is an indirect ACLY inhibitor,and it has recently been approved by the FDA as an additional therapeutic option in high-risk hypercholesterolemia patients unable to meet goals with standard *** this work,we identified a series of novel long-chain alkenyl diacids as potent direct ACLY inhibitors,and comprehensive structure-activity relationship analysis showed that compound 18f was the most potent ACLY inhibitor with an IC50 value of 1.5μmol/*** ester formation of 18f gave a new series of compounds such as 25f that maintained ACLY inhibitory activity and improved antitumor cell proliferation effects.

关键词： Alkenyl diacid derivatives Cancer ACLY inhibitors Acetyl-CoA Structure-activity relationships

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Recent advances in developing active targeting and multi-functional drug delivery systems via bioorthogonal chemistry

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Signal Transduction and Targeted Therapy 2023年第1期8卷 13-37页

作者： Wenzhe Yi Ping Xiao Xiaochen Liu Zitong Zhao Xiangshi Sun Jue Wang Lei Zhou Guanru Wang Haiqiang Cao Dangge Wang Yaping Li State Key laboratory of Drug Research&Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Yantai Key laboratory of nanomedicine&Advanced Preparations Yantai Institute of Materia MedicaYantai 264000China Shandong laboratory of Yantai Drug Discovery Bohai Rim Advanced Research Institute for Drug DiscoveryYantai 264000China

Bioorthogonal chemistry reactions occur in physiological conditions without interfering with normal physiological *** metabolic engineering,bioorthogonal groups can be tagged onto cell membranes,which selectively attach to cargos with paired groups via bioorthogonal *** to its simplicity,high efficiency,and specificity,bioorthogonal chemistry has demonstrated great application potential in drug *** the one hand,bioorthogonal reactions improve therapeutic agent delivery to target sites,overcoming off-target *** the other hand,nanoparticles and biomolecules can be linked to cell membranes by bioorthogonal reactions,providing approaches to developing multi-functional drug delivery systems(DDSs).In this review,we first describe the principle of labeling cells or pathogenic microorganisms with bioorthogonal *** then highlight recent breakthroughs in developing active targeting DDSs to tumors,immune systems,or bacteria by bioorthogonal chemistry,as well as applications of bioorthogonal chemistry in developing functional bio-inspired DDSs(biomimetic DDSs,cell-based DDSs,bacteria-based and phage-based DDSs)and ***,we discuss the difficulties and prospective direction of bioorthogonal chemistry in drug *** expect this review will help us understand the latest advances in the development of active targeting and multi-functional DDSs using bioorthogonal chemistry and inspire innovative applications of bioorthogonal chemistry in developing smart DDSs for disease treatment.

关键词： functional orthogonal breakthrough

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High stability three-dimensional porous PtSn nano-catalyst for ethanol electro-oxidation reaction

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Chinese Chemical Letters 2020年第9期31卷 2491-2494页

作者： Yue Sun Haiyan Xiang Huimin Li Gang Yu Hong Chen Song Liu Institute of Chemical Biology and nanomedicine(ICBN) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082China School of Materials Science and Energy Engineering Foshan UniversityFoshan 528000China

In addition to the theoretical research,direct ethanol fuel cells have great potential in practical *** performance of direct ethanol fuel cells largely depends on the *** electrocatalysts have been promising candidates for advancing direct ethanol fuel cells for its high catalytic activity and great ***,a PtSn catalyst with unique three-dimensional porous nanostructure has been designed and synthesized via a two-step liquid phase reduction *** formed a self-supporting framework in PtSn alloy particles(~3.5 nm).In ethanol electro-oxidation reaction,the PtSn catalyst exhibited high mass activity and excellent recycling time compared with that of Pt/*** the morphology characterization before and after potential cycling,the PtSn alloy-based nano-catalyst showed good *** PtSn catalysts effectively avoid structural instability due to the external carriers,and prolong the leaching time of *** addition,the introduction of a certain amount of Sn can also solve the poisoning phenomenon of active sites on Pt *** design strategy of porous alloy nano-catalyst sheds light on its applications in direct ethanol fuel cells.

关键词： PtSn Porous structure Direct ethanol fuel cell Ethanol electro-oxidation Stability

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Distance-basedα-amylase biosensor fabricated with amylopectin-coated mesoporous membrane

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Chinese Chemical Letters 2024年第1期35卷 446-450页

作者： Binglu Zhao Mashooq Khan Yulin Liu Wenjun Tai Chongyang Mu Wenli Wu Mei Zhao Yaohong Ma Li Yu Jin-Ming Lin Qiongzheng Hu Qilu University of Technology(Shandong Academy of Sciences) Shandong Analysis and Test CenterJi’nan 250014China School of Pharmaceutical Sciences Qilu University of Technology(Shandong Academy of Sciences)Ji’nan 250014China Key laboratory of Colloid and Interface Chemistry Shandong UniversityMinistry of EducationJi’nan 250100China Key laboratory for biosensors of Shandong Province Biology InstituteQilu University of Technology(Shandong Academy of Sciences)Ji’nan 250353China Beijing Key laboratory of Microanalytical Methods and Instrumentation MOE Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical BiologyDepartment of ChemistryTsinghua UniversityBeijing 100084China

Paper-based biosensors are widely employed in point-of-care testing(POCT)due to their convenience,portability,low cost,and ease of *** study reports an integrated distance-based paper biosensor fabricated with a mesoporous membrane coated with stimuli-responsive *** detection ofα-amylase(AMY)using amylopectin-coated mesoporous membrane is demonstrated as an *** introducing the AMY solution,it is observed that the aqueous solution flows along the paper strip due to AMY-catalyzed hydrolysis of *** flow distance is proportional to the concentration of AMY with a detection limit as low as 4 mU/*** addition,the detection of AMY is demonstrated in human ***,the inhibitory effect of acarbose on AMY is *** reagent-free and disposable biosensor allows single-step rapid detection of the *** approach is very promising for the development of user-friendly,equipment-free,and cost-effective biosensors with remarkable sensitivity and excellent selectivity for disease diagnosis and hypoglycemic drug screening.

关键词： Paper biosensor α-Amylase Stimuli-responsive polymer Mesoporous membrane Distance Point-of-care testing

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An ultra-sensitive biosensor for circulating microRNA detection with Fe single-atom enhanced cathodic luminol-O_(2) electrochemiluminescence

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Nano Research 2024年第9期17卷 7926-7934页

作者： Yudie Sun Yunxiang Han Mingyue Wang Mingfu Ye Konglin Wu Kui Zhang School of Chemistry and Chemical Engineering Anhui University of TechnologyMa'anshan 243032China Key laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science MOEQingdao University of Science and TechnologyQingdao 266042China Engineering Research Center of Biofilm Water Purification and Utilization Technology of Ministry of Education Anhui University of TechnologyMa'anshan 243032China

Circulating microRNAs(miRNAs)play a pivotal role in the occurrence and development of acute myocardial infarction(AMI),and precise detection of them holds significant clinical *** development of luminol-based luminophores in the field of electrochemiluminescence(ECL)for miRNA detection has been significant,while their effectiveness is hindered by the instability of co-reactant hydrogen peroxide(H_(2)O_(2)).In this work,an iron single-atom catalyst(Fe-PNC)was employed for catalyzing the luminol-O_(2) ECL system to achieve ultra-sensitive detection of myocardial *** miRNA triggers a hybridization chain reaction(HCR),resulting in the generation of a DNA product featuring multiple sticky ends that facilitate the attachment of Fe-PNC probes to the electrode *** Fe-PNC catalyst exhibits high promise and efficiency for the oxygen reduction reaction(ORR)in electrochemical energy conversion *** resulting ECL biosensor allowed ultrasensitive detection of myocardial miRNA with a low detection limit of 0.42 fM and a wide linear range from 1 fM to 1.0 ***,it demonstrates exceptional performance when evaluated using serum samples collected from patients with *** work expands the application of single-atom catalysis in ECL sensing and introduces novel perspectives for utilizing ECL in disease diagnosis.

关键词： circulating miRNAs single-atom catalyst luminol-O_(2) electrochemiluminescence hybridization chain reaction

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Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment

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Microsystems & Nanoengineering 2021年第2期7卷 131-142页

作者： Jiaru Fang Xinwei Wei Hongbo Li Ning Hu Xingxing Liu Dongxin Xu Tao Zhang Hao Wan Ping Wang Xi Xie The First Affiliated Hospital of Sun Yat-Sen University School of Electronics and Information TechnologyGuangdong Province Key Laboratory of Display Material and TechnologySun Yat-sen UniversityGuangzhou510006China biosensor National Special laboratory Key Laboratory of Biomedical Engineering of Ministry of EducationDepartment of Biomedical EngineeringZhejiang UniversityHangzhou310027China State Key laboratory of Transducer Technology Chinese Academy of SciencesShanghai200050China School of Biomedical Engineering Sun Yat-sen UniversityGuangzhou510006China

Cardiovascular diseases have emerged as a significant threat to human ***,drug development is a time-consuming and costly process,and few drugs pass the preclinical assessment of safety and *** existing patch-clamp,Ca2+imaging,and microelectrode array technologies in cardiomyocyte models for drug preclinical screening have suffered from issues of low throughput,limited long-term assessment,or inability to synchronously and correlatively analyze electrical and mechanical ***,we develop a high-content,dose-quantitative and time-dependent drug assessment platform based on an electrical-mechanical synchronized(EMS)biosensing *** microfabricated EMS can record both firing potential(FP)and mechanical beating(MB)signals from cardiomyocytes and extract a variety of characteristic parameters from these two signals(FP–MB)for further *** system was applied to test typical ion channel drugs(lidocaine and isradipine),and the dynamic responses of cardiomyocytes to the tested drugs were recorded and *** high-throughput characteristics of the system can facilitate simultaneous experiments on a large number of ***,a database of various cardiac drugs can be established by heat map analysis for rapid and effective screening of *** EMS biosensing system is highly promising as a powerful tool for the preclinical development of new medicines.

关键词： electrical consuming patch

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Immune checkpoint inhibition mediated with liposomal nanomedicine for cancer therapy

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Military Medical Research 2024年第1期11卷 98-114页

作者： Guang-Long Ma Wei-Feng Lin Faculty of Medicine Centre for Cancer ImmunologyUniversity of SouthamptonSouthampton SO166YDUK Department of Molecular Chemistry and Materials Science Weizmann Institute of Science76100 RehovotIsrael Key laboratory of Bio-Inspired Smart Interfacial Science and Technology of Ministry of Education School of ChemistryBeihang UniversityBeijing 100191China

Immune checkpoint blockade(ICB)therapy for cancer has achieved great success both in clinical results and on the *** the same time,success drives more attention from scientists to improve ***,only a small portion of patients are responsive to this therapy,and it comes with a unique spectrum of side effects termed immunerelated adverse events(irAEs).The use of nanotechnology could improve ICBs’delivery to the tumor,assist them in penetrating deeper into tumor tissues and alleviate their *** nanomedicine has been investigated and used for decades,and is well-recognized as the most successful nano-drug delivery *** successful combination of ICB with liposomal nanomedicine could help improve the efficacy of ICB *** this review,we highlighted recent studies using liposomal nanomedicine(including new emerging exosomes and their inspired nanovesicles)in associating ICB therapy.

关键词： Liposome Exosome Immune checkpoint blockade(ICB)

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Legumain-triggered aggregable gold nanoparticles for enhanced intratumoral retention

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Chinese Chemical Letters 2024年第7期35卷 388-393页

作者： Zhi Li Wenpei Li Shaoping Jiang Chuan Hu Yuanyu Huang Maxim Shevtsov Huile Gao Shaobo Ruan Advanced Research Institute of Multidisciplinary Sciences School of Life ScienceBeijing Institute of TechnologyBeijing 100081China Key laboratory of Drug Targeting and Drug Delivery System West China School of PharmacySichuan UniversityChengdu 610041China Institute of Cytology of Russian Academy of Sciences(RAS) St.Petersburg 194064Russia

Insufficient intratumoral retention of nanomedicines remains the major challenge for broad implementation in clinical ***,we proposed a legumain-triggered aggregable gold nanoparticle(GNP)delivery platform(GNPs-A&C).GNPs-A&C could form intratumoral or intracellular aggregates in response to the overexpressed *** aggregates with size increase not only could reduce back-flow from interstitial space to peripheral bloodstream but also could restrict the cellular exocytosis,leading to enhanced intratumoral *** vitro studies demonstrated that GNPs-A&C possessed an excellent legumain responsiveness and the increased size was closely relevant with legumain *** vivo studies demonstrated GNPs-A&C possessed slower clearance rate and much higher intratumoral retention within legumain-overexpressed tumor compared to non-aggregable NPs,regardless of intravenous or intratumoral *** importantly,this delivery platform significantly improved the chemotherapeutic effect of doxorubicin(DOX)towards subcutaneous xenograft C6 *** effectiveness of this stimulus-responsive aggregable delivery system provides a thinking for designing more intelligent size-tunable nanomedicine that can substantially improve intratumoral retention.

关键词： Legumain Size-tunable Enhanced retention Stimulus-responsive nanomedicine

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Targeting peptide-decorated biomimetic lipoproteins improve deep penetration and cancer cells accessibility in solid tumor

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Acta Pharmaceutica Sinica B 2020年第3期10卷 529-545页

作者： Tao Tan Yuqi Wang Jing Wang Zhiwan Wang Hong Wang Haiqiang Cao Jie Li Yaping Li Zhiwen Zhang Siling Wang School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China State Key laboratory of Drug Research&Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Yantai Key laboratory of nanomedicine&Advanced Preparations Yantai Institute of Materia MedicaYantai 264000China

The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer ***,we designed a targeting peptide-decorated biomimetic lipoprotein(termed as BL-RD)to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor,thereby improving the combinational chemophotodynamic therapy of triple negative breast ***-RD was composed of phospholipids,apolipoprotein A1 mimetic peptide(PK22),targeting peptide-conjugated cytotoxic mertansine(RM)and photodynamic agents of DiIC18(5)(DiD).The counterpart biomimetic lipoprotein system without RM(termed as BL-D)was fabricated as *** BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer *** intravenous injection,they can be specifically accumulated at tumor *** comparing to the counterpart BLD,BL-RD displayed superior capability to permeate across the tumor mass,extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor,thus producing noticeable depression of the tumor *** together,BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.

关键词： Lipoprotein Drug delivery Tumor penetration Nanoparticles Cancer therapy

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