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A novel marine-derived anti-acute kidney injury agent targeting peroxiredoxin 1 and its nanodelivery strategy based on ADME optimization

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3232-3250页

作者： Ping Yu Tanwei Gu Yueyang Rao Weimin Liang Xi Zhang Huanguo Jiang Jindi Lu Jianglian She Jianmin Guo Wei Yang Yonghong Liu yingfeng tu Lan Tang Xuefeng Zhou Guangdong Provincial Key Laboratory of New Drug Screening Guangdong-Hong Kong-Macao Joint Laboratory for New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaSouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China NMPA Key Laboratory for Research and Evaluation of Drug Metabolism School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Guangdong Lewwin Pharmaceutical Research Institute Co. Ltd.Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and ResearchGuangdong Engineering Research Center for Innovative Drug Evaluation and ResearchGuangzhou 510990China

Insufficient therapeutic strategies for acute kidney injury(AKI)necessitate precision therapy targeting its *** study reveals the new mechanism of the marine-derived anti-AKI agent,piericidin glycoside S14,targeting peroxiredoxin 1(PRDX1).By binding to Cys83 of PRDX1 and augmenting its peroxidase activity,S14 alleviates kidney injury efficiently in Prdx1-overexpression(Prdx1-OE)***,S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS *** to the limited druggability of S14 with low bioavailability(2.6%)and poor renal distribution,a pH-sensitive kidney-targeting dodecanaminechitosan nanoparticle system is constructed to load S14 for precise treatment of AKI.L-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1(Kim-1)-overexpressed *** developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 *** encapsulation with micelles,the AUC_(0-t),half-life time,and renal distribution of S14 increase 2.5-,1.8-,and 3.1-fold,*** main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDPglycosyltransferase(UGT)-mediated *** summary,this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology,thereby driving advancements in marine drug development for AKI.

关键词： Acute kidney injury Piericidin glycoside Peroxiredoxin 1 Nanodrug Kim-1 targeted ADME Marine drug Druggability

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Controlling Morphology of Active Layer by tuning Coplanarity of the Centrality in Acceptor-Donor-Acceptor Small Molecules for Photovoltaic Application

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Chinese Journal of Chemistry 2013年第11期31卷 1439-1448页

作者： Pan Zhang Chao Li Yue Zhao Yaowen Li yingfeng tu Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application Department of Polymer Science and Engineering College of Chemistry Chemical Engineering and Materials Science Soochow University Suzhou Jiangsu 215123 China

A series of acceptor-donor-acceptor alternative small molecules were synthesized containing electron-donating central building moieties of phenothiazine, 2,7-carbazole and thieno[3,4-b]thiophene and electron-accepting moie- ties of tetrazine on both sides. The various conformations of the central blocks, with the coplanarity in an order of phenothiazine〈2,7-carbazole〈thieno[3,4-b]thiophene, have an obvious influence on the optical, electrochemical property and the crystallinity of small molecule. In addition, the blend films between small molecule and （6,6）-phenyl-C6rbutyric acid methyl ester offered significantly various morphologies, changing from uniform sur- face to interpenetrated networks. As a result, the bulk heterojunction photovoltaic devices based on the three small molecules provided varied performance, and the highest coplanar molecule based device exhibited the best photo- voltaic performance.

关键词： acceptor-donor-acceptor small molecules central blocks coplanarity morphology

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Janus Polymerization:A One-Shot Approach towards Amphiphilic Multiblock Poly(ester-acetal)s Directly from 1,3-Dioxolane withε-Caprolactone

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Chinese Journal of Chemistry 2022年第6期40卷 705-712页

作者： Huan Qiu Ting Shen Zhening Yang Feng Wu Xiaohong Li yingfeng tu Jun Ling MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhouZhejiang 310027China College of Chemistry Chemical Engineering and Materials ScienceSoochow UniversitySuzhouJiangsu 215123China

Janus polymerization consists of anionic and cationic ring opening polymerizations(AROP and CROP)at the two ends of a single propagating polymer chain,followed by a self-triggered chain extension generating multiblock copolymers(MBCPs)in one *** the contribution,Janus polymerization by Tm(OTf)_(3) or Er(OTf)_(3) catalyst with an epoxy initiator is applied to synthesize MBCPs of semi-crystalline poly(ε-caprolactone)(PCL)blocks from coordinated AROP and poly(1,3-dioxolane-co-ε-caprolactone)(P(DO-co-CL))blocks from CROP of DO with ***,amorphous random copolymers[P(DO-r-CL)]are synthesized as control by employing other rare earth triflates[RE(OTf)_(3),RE=Y,Nd,Gd and Lu]as catalysts or in the absence of an initiator via *** account of the distinguishable chemical structures and thermal properties between Janus MBCPs and cationic random copolymers,Janus features are confirmed including the CROP and AROP at a single propagating *** resultant amphiphilic copolymers self-assemble to nanoparticles in aqueous solution with designable diameters with the corresponding ratios of hydrophilic and hydrophobic *** exhibit good shape memory properties with appropriate deformation temperature close to human body's,providing a prospect on the applications in biomedical devices.

关键词： Janus polymerization Ring-opening polymerization Multiblock copolymers Homogeneous catalysis(?)Lanthanides

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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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心力衰竭中利尿剂抵抗机制研究新进展

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临床心血管病杂志 2024年第7期40卷 584-588页

作者：曲连卉邵薪诺徐珂涂应锋哈尔滨医科大学附属第一医院心内科哈尔滨150007

利尿剂是急性心力衰竭(心衰)的一线治疗药物,也是临床上缓解充血症状的基石。利尿剂抵抗致使心衰患者的再入院率和病死率增加,是临床治疗的一大难点,其机制目前尚不明确。最新研究机制包括腹内高压、盆腔化学感受器等,针对这些机制已有... 详细信息

利尿剂是急性心力衰竭(心衰)的一线治疗药物,也是临床上缓解充血症状的基石。利尿剂抵抗致使心衰患者的再入院率和病死率增加,是临床治疗的一大难点,其机制目前尚不明确。最新研究机制包括腹内高压、盆腔化学感受器等,针对这些机制已有相应的治疗手段,所涉及的有机阴离子转运多肽2B1、肾脏钠再摄取转运体基因变异机制也将大大开拓利尿剂抵抗治疗的新思路。本文将对可能产生利尿剂抵抗的机制进行梳理以及对利尿剂抵抗的新治疗手段进行概括,以期全面了解利尿剂抵抗。

关键词：利尿剂抵抗有机阴离子转运多肽2B1 腹内高压盆腔化学感受器肾脏钠再摄取转运体基因

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Medical micro-and nanomotors in the body

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Acta Pharmaceutica Sinica B 2023年第2期13卷 517-541页

作者： Huaan Li Fei Peng Xiaohui Yan Chun Mao Xing Ma Daniela A.Wilson Qiang He yingfeng tu Department of Pharmacy Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China School of Pharmaceutical Science Guangdong Provincial Key Laboratory of New Drug ScreeningSouthern Medical UniversityGuangzhou 510515China School of Materials Science and Engineering Sun Yat-Sen UniversityGuangzhou 510275China State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics&Centre for Molecular Imaging and Translational Medicine School of Public HealthXiamen UniversityXiamen 361005China National and Local Joint Engineering Research Center of Biomedical Functional Materials School of Chemistry and Materials ScienceNanjing Normal UniversityNanjing 210023China Sauvage Laboratory for Smart Materials School of Materials Science and EngineeringHarbin Institute of Technology(Shenzhen)Shenzhen 518055China Institute for Molecules and Materials Radboud UniversityNijmegen6525 AJthe Netherlands Key Laboratory of Microsystems and Microstructures Manufacturing(Ministry of Education) School of Medicine and HealthHarbin Institute of TechnologyHarbin 150080China

Attributed to the miniaturized body size and active mobility,micro-and nanomotors(MNMs)have demonstrated tremendous potential for medical ***,from bench to bedside,massive efforts are needed to address critical issues,such as cost-effective fabrication,on-demand integration of multiple functions,biocompatibility,biodegradability,controlled propulsion and in vivo ***,we summarize the advances of biomedical MNMs reported in the past two decades,with particular emphasis on the design,fabrication,propulsion,navigation,and the abilities of biological barriers penetration,biosensing,diagnosis,minimally invasive surgery and targeted cargo *** perspectives and challenges are discussed as *** review can lay the foundation for the future direction of medical MNMs,pushing one step forward on the road to achieving practical theranostics using MNMs.

关键词： Micro-and nanomotors Function integration Controlled propulsion In vivo navigation Biomedical applications Minimally invasive microsurgery Biosensing Biological barrier penetration

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Polymer solar cells with an inverted device configuration using polyhedral oligomeric silsesquioxane-[60]fullerene dyad as a novel electron acceptor

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Science China Chemistry 2012年第5期55卷 749-754页

作者： ZHANG Wen-Bin tu yingfeng SUN Hao-Jan YUE Kan GONG Xiong CHENG Stephen Z. D. College of Polymer Science and Polymer Engineering The University of Akron Akron OH 44325 USA College of Chemistry Chemical Engineering and Materials Science Soochow University Suzhou 215123 China

A polyhedral oligomeric silsesquioxane-[60]fullerene (POSS-C60) dyad was designed and used as a novel electron acceptor for bulk heterojunction (BHJ) polymer solar cells (PSCs) with an inverted device configuration. The studies of time-resolved photoinduced absorption of the pristine thin film of poly[(4,4'-bis(2-ethylhexyl)dithieno[3,2-b:2',3'-d]silole)-2,6-diyl-alt-(4,7-bis (2-thienyl)-2,1,3-benzothiadiazole)-5,5'-diyl] (SiPCPDTBT) and the composite thin film of SiPCPDTBT:POSS-C60 indicated efficient electron transfer from SiPCPDTBT to POSS-C60 with inhibited back-transfer. BHJ PSCs made by SiPCPDTBT mixed with POSS-C60 yielded the power conversion efficiencies (PCEs) of 1.50%. Under the same operational conditions, PCEs observed from BHJ PSCs made by SiPCPDTBT mixed with [6,6]-phenyl-C61-butyric acid methyl ester were 0.92%. These results demonstrated that POSS-C60 is a potentially good electron acceptor for inverted BHJ PSCs.

关键词： electron acceptor polyhedral oligomeric silsesquioxane fullerene polymer solar cells inverted device structure

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Mechanism study and molecular design in controlled/“living” radical polymerization

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Science China Chemistry 2010年第8期53卷 1605-1619页

作者： tu yingfeng,CHENG ZhenPing,ZHANG ZhengBiao,ZHU Jian,ZHANG Wei,ZHOU NianChen,NI PeiHong & ZHU XiuLin College of Chemistry,Chemical Engineering and Materials Science,Soochow University,Suzhou 215123,China College of Chemistry Chemical Engineering and Materials Science Soochow University Suzhou China

This tutorial review summarizes recent progress in the research field of controlled/"living" radical polymerization (CLRP) from Soochow *** present paper gives a broad overview of the mechanism study and molecular design in *** mechanism study in CLRP aided by microwave,initiated by γ-radiation at low temperature,mediated by iron,in reversible addition-fragmentation chain transfer (RAFT) polymerization and the mechanism transfer between different CLRP processes are reviewed and *** molecular design in CLRP,especially in RAFT polymerization for mechanism study,and in achieving tailor-made functional polymers is studied and discussed in the later part.

关键词： controlled/"living" radical polymerization atom transfer radical polymerization reversible addition-fragmentation chain transfer polymerization molecule design mechanism study

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三元乙丙橡胶混炼胶的组分及配方分析

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橡胶工业 2024年第8期71卷 624-629页

作者：吴文宁张文浩汪胜陆成华孙子渊李晓虹屠迎锋苏州大学材料与化学化工学部江苏苏州215123 苏州华东橡胶工业有限公司江苏苏州215000

对三元乙丙橡胶(EPDM)混炼胶的各组分进行分离并对配方进行分析。以正庚烷溶解EPDM混炼胶,将其有机组分与无机组分分离;有机组分在甲醇中沉淀后经二氯甲烷抽提,将EPDM与石蜡油分离;以盐酸溶解无机组分,将碳酸盐和氧化锌与白炭黑分离;采... 详细信息

对三元乙丙橡胶(EPDM)混炼胶的各组分进行分离并对配方进行分析。以正庚烷溶解EPDM混炼胶,将其有机组分与无机组分分离;有机组分在甲醇中沉淀后经二氯甲烷抽提,将EPDM与石蜡油分离;以盐酸溶解无机组分,将碳酸盐和氧化锌与白炭黑分离;采用核磁共振氢谱、核磁共振扩散序谱、傅里叶红外光谱、X-射线衍射谱和X-射线光电子能谱,对各组分进行定性和定量分析,建立一套EPDM混炼胶组分的分析方法,有助于EPDM混炼胶的生产过程质量监控和配方改进。

关键词：三元乙丙橡胶混炼胶组分配方测试与分析

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Bladder microenvironment actuated proteomotors with ammonia amplification for enhanced cancer treatment

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药学学报:英文版 2023年第9期13卷 3862-3875页

作者： Hao Tian Juanfeng Ou Yong Wang Jia Sun Junbin Gao Yicheng Ye Ruotian Zhang Bin Chen Fei Wang Weichang Huang Huaan Li Lu Liu Chuxiao Shao Zhili Xu Fei Peng yingfeng tu NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Pharmacy Zhujiang HospitalSouthern Medical UniversityGuangzhou 510282China Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui Central Laboratory of Lishui People’s HospitalThe Sixth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000China Department of Ultrasound Institute of Ultrasound in Musculoskeletal Sports MedicineGuangdong Second Provincial General HospitalGuangzhou 510317China School of Materials Science and Engineering Sun Yat-Sen UniversityGuangzhou 510275China

Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical ***,motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain ***,swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia *** decomposing urea into carbon dioxide and ammonia,the designed proteomotors are endowed with self-propulsive capability,which leads to improved internalization and enhanced penetration in *** a glutamine synthetase inhibitor,the loaded L-methionine sulfoximine further prevents the conversion of toxic ammonia into non-toxic glutamine in both tumor and stromal cells,resulting in local ammonia *** intravesical instillation,the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse *** envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.

关键词： Swimming proteomotors Enhanced diffusion Glutamine synthetase Ammonia amplification Biocompatibility Penetration Retention Bladder microenvironment

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