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Poly(ethylene glycol) conjugated nano-graphene oxide for photodynamic therapy

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Science China Chemistry 2010年第11期53卷 2265-2271页

作者： Pilger FRANK Institute for Advanced Materials and Nano biomedicine(iNANO) Tongji University

A novel methoxy-poly(ethylene glycol) modified nano-graphene oxide(NGO-mPEG) was designed and synthesized as a photosensitizer(PS) carrier for photodynamic therapy of *** with a size below 200 nm was prepared using a modified Hummers' *** was observed by AFM to exhibit a structure with single-layer graphene oxide sheets down to a few nanometers in *** mPEG conjugation of NGO(NGO-mPEG) was found to enhance solubility in cell culture *** apparent cytotoxicity of the NGO-mPEG was observed towards MCF-7 carcinoma cell *** phthalocyanine(ZnPc),a photosensitizer for photodynamic therapy,was loaded in the NGO-PEG through π-π stacking and hydrophobic interactions,with the drug loading efficiency up to 14 wt%.Hydrophobic ZnPc was internalized in MCF-7 cells,exhibiting a pronounced phototoxicity in the cells under Xe light *** results indicate a great potential of NGO-mPEG for photodynamic therapy of cancer.

关键词： nano-graphene oxide photodynamic therapy photosensitizer drug delivery biomedical application

Double knock-in pig models with elements of binary Tet-On and phiC31 integrase systems for controllable and switchable gene expression

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Science China(Life Sciences) 2022年第11期65卷 2269-2286页

作者： Qin Jin Xiaoyu Yang Shixue Gou Xiaoyi Liu Zhenpeng Zhuang Yanhui Liang Hui Shi Jiayuan Huang Han Wu Yu Zhao Zhen Ouyang Quanjun Zhang Zhaoming Liu Fangbing Chen Weikai Ge Jingke Xie Nan Li Chengdan Lai Xiaozhu Zhao Jiaowei Wang Meng Lian Lei Li Longquan Quan Yinghua Ye Liangxue Lai Kepin Wang CAS Key Laboratory of Regenerative Biology Joint School of Life SciencesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou Medical UniversityGuangzhou 510530China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine Centre for Regenerative Medicine and HealthHong Kong Institute of Science and InnovationGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Sanya institute of Swine resource Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesHainan Provincial Research Center of Laboratory AnimalsSanya 572000China Research Unit of Generation of Large Animal Disease Models Chinese Academy of Medical Sciences(2019RU015)Guangzhou 510530China University of Chinese Academy of Sciences Beijing 100049China Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) Guangzhou 510005China Guangdong Provincial Key Laboratory of Laboratory Animals Guangdong Laboratory Animals Monitoring InstituteGuangzhou 510633China Guangdong Provincial Key Laboratory of Large Animal models for biomedicine Wuyi UniversityJiangmen 529020China

Inducible expression systems are indispensable for precise regulation and in-depth analysis of biological *** Tet-On system has been widely employed to regulate transgenic expression by *** pig models with tetracycline regulatory elements were generated through random *** process often resulted in uncertain expression and unpredictable phenotypes,thus hindering their ***,by precise knock-in of binary Tet-On 3G elements into Rosa26 and Hipp11 locus,respectively,a double knock-in reporter pig model was *** characterized excellent properties of this system for controllable transgenic expression both in vitro and in *** att P sites were arranged to flank the td Tomato to switch reporter *** or multiple gene replacement was efficiently and faithfully achieved in fetal fibroblasts and nuclear transfer *** display the flexible application of this system,we generated a pig strain with Dox-inducing h KRASexpression through phiC31 integrase-mediated cassette *** eight months of Dox administration,squamous cell carcinoma developed in the nose,mouth,and scrotum,which indicated this pig strain could serve as an ideal large animal model to study ***,the established pig models with controllable and switchable transgene expression system will provide a facilitating platform for transgenic and biomedical research.

关键词： double knock-in Tet-On system phiC31-mediated cassette exchange pig model hKRASG12D-related tumorigenesis

Photochemical Nitration of Protected Anilines by 5-Methyl-1,4-dinitroimidazole

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中国化学:英文版 2023年第13期41卷 1589-1593页

作者： Xinlong Fan Yue Zhao Lei Liu Huan Wang State Key Laboratory of Coordination Chemistry Chemistry and Biomedicine Innovation Center of Nanjing UniversityJiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringNanjing UniversityNanjingJiangsu210023 China

Nitroanilines are important building blocks in pharmaceuticals,materials and *** methods for anilines under mild conditions are highly ***,we report a photochemical method for the nitration of anilines bearing various protecting groups by 5-methyl-1,4-dinitroimidazole as a new type of nitro *** method is light-controlled and proceeds under mild reaction conditions with high ***-,Ts-and alkyl-protected anilines are all well nitrated with good functional group tolerance.

关键词： Aniline Nitration Photocatalysis Photochemistry Dinitroimidazole Nitroaniline Peptidomimetics Radical reactions

Rac GTPases:domain-specific functions in neuronal development

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Neural Regeneration Research 2019年第8期14卷 1367-1368页

作者： Steffen Norgaard Roger Pocock Development and Stem Cells program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology Monash University Melbourne Victoria Australia Biotech Research and Innovation Centre University of Copenhagen Copenhagen Denmark

Understanding fundamental mechanisms governing axon outgrowth and guidance can inform the development of therapeutic strategies to restore neuronal function damaged though injury or disease. Axons navigate the extracellular environment by responding to guidance cues that bind to cell surface receptors to relay information intracellularly via Rho GTPase family members, including the Rac GTPases.

关键词： Rac GTPases domain-specific functions neuronal development

Rational multivalency construction enables bactericidal effect amplification and dynamic biomaterial design

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The Innovation 2023年第5期4卷 59-68页

作者： Xu Chen Xinrui Li Wenbo He Miao Wang Ang Gao Liping Tong Shun Guo Huaiyu Wang Guoqing Pan Institute for Advanced Materials School of Materials Science and EngineeringJiangsu UniversityZhenjiang 212013China Institute of biomedicine and Biotechnology Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

The multivalency of bioligands in living systems brings inspiration for not only the discovery of biological mechanisms but also the design of extracellular matrix(ECM)-mimicking ***,designing controllable multivalency construction strategies is still ***,we synthesized a series of well-defined multivalent antimicrobial peptide polymers(mAMPs)by clicking ligand molecules onto polymers prepared by reversible addition-fragmentation chain transfer *** multiple cationic ligands in the mAMPs could enhance the local disturbance of the anionic phospholipid layer of the bacterial membrane through multivalent binding,leading to amplification of the bactericidal *** addition to multivalency-enhanced antibacterial activity,mAMPs also enable multivalency-assisted hydrogel fabrication with an ECM-like dynamic *** resultant hydrogel with self-healing and injectable properties could be successfully employed as an antibacterial biomaterial scaffold to treat infected skin *** multivalency construction strategy presented in this work provides new ideas for the biomimetic design of highly active and dynamic biomaterials for tissue repair and regeneration.

关键词： healing enable dynamic

SynergyFinder Plus:Toward Better Interpretation and Annotation of Drug Combination Screening Datasets

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Genomics, Proteomics & Bioinformatics 2022年第3期20卷 587-596页

作者： Shuyu Zheng Wenyu Wang Jehad Aldahdooh Alina Malyutina Tolou Shadbahr Ziaurrehman Tanoli Alberto Pessia Jing Tang Research program in Systems Oncology Faculty of MedicineUniversity of HelsinkiHelsinki 00290Finland

Combinatorial therapies have been recently proposed to improve the efficacy of anticancer treatment. The Synergy Finder R package is a software used to analyze pre-clinical drug combination datasets. Here, we report the major updates to the Synergy Finder R package for improved interpretation and annotation of drug combination screening results. Unlike the existing implementations, the updated Synergy Finder R package includes five main innovations. 1) We extend the mathematical models to higher-order drug combination data analysis and implement dimension reduction techniques for visualizing the synergy landscape. 2) We provide a statistical analysis of drug combination synergy and sensitivity with confidence intervals and P values. 3)We incorporate a synergy barometer to harmonize multiple synergy scoring methods to provide a consensus metric for synergy. 4) We evaluate drug combination synergy and sensitivity to provide an unbiased interpretation of the clinical potential. 5) We enable fast annotation of drugs and cell lines, including their chemical and target information. These annotations will improve the interpretation of the mechanisms of action of drug combinations. To facilitate the use of the R package within the drug discovery community, we also provide a web server at www.s *** as a user-friendly interface to enable a more fexible and versatile analysis of drug combination data.

关键词： SynergyFinder Drug combination Synergy modeling Drug discovery Drug combination sensitivity analysis

Genome-scale metabolic modeling in antimicrobial pharmacology

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Engineering Microbiology 2022年第2期2卷 21-28页

作者： Yan Zhu Jinxin Zhao Jian Li Infection program and Department of Microbiology Biomedicine Discovery InstituteMonash University19 Innovation WalkMelbourneVictoria 3800Australia

The increasing antimicrobial resistance has seriously threatened human health worldwide over the last three *** severe medical crisis and the dwindling antibiotic discovery pipeline require the development of novel antimicrobial treatments to combat life-threatening infections caused by multidrug-resistant micro-bial ***,the detailed mechanisms of action,resistance,and toxicity of many antimicrobials remain uncertain,significantly hampering the development of novel ***-scale metabolic model(GSMM)has been increasingly employed to investigate microbial *** this review,we discuss the latest progress of GSMM in antimicrobial pharmacology,particularly in elucidating the complex interplays of multiple metabolic pathways involved in antimicrobial activity,resistance,and *** also highlight the emerging areas of GSMM applications in modeling non-metabolic cellular activities(e.g.,gene expression),identi-fication of potential drug targets,and integration with machine learning and pharmacokinetic/pharmacodynamic ***,GSMM has significant potential in elucidating the critical role of metabolic changes in antimi-crobial pharmacology,providing mechanistic insights that will guide the optimization of dosing regimens for the treatment of antimicrobial-resistant infections.

关键词： Genome-scale metabolic model Flux balance analysis Antimicrobial pharmacology Antimicrobial resistance Toxicity Pharmacokinetic/pharmacodynamic model

Overcoming the obstacles of current photodynamic therapy in tumors using nanoparticles

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Bioactive Materials 2022年第2期7卷 20-34页

作者： Donghyun Lee Soonmin Kwon Seok-young Jang Eunyoung Park Yeeun Lee Heebeom Koo Department of Medical Life Sciences Department of Biomedicine&Health Sciencesand Catholic Photomedicine Research InstituteCollege of MedicineThe Catholic University of Korea222 Banpo-daeroSeocho-guSeoul06591Republic of Korea

Photodynamic therapy(PDT)has been applied in clinical treatment of tumors for a long ***,insufficient supply of pivotal factors including photosensitizer(PS),light,and oxygen in tumor tissue dramatically reduces the therapeutic efficacy of *** have received an influx of attention as drug carriers,and recent studies have demonstrated their promising potential to overcome the obstacles of PDT in tumor *** optimization for passive targeting,ligand modification for active targeting,and stimuli-responsive release achieved efficient delivery of PS to tumor *** trials using upconversion NPs,two-photon lasers,X-rays,and bioluminescence have provided clues for efficient methods of light delivery to deep *** have been made to overcome unfavorable tumor microenvironments via artificial oxygen generation,Fenton reaction,and combination with other chemical *** this review,we introduce these creative approaches to addressing the hurdles facing PDT in *** particular,the studies that have been validated in animal experiments are preferred in this review over proof-of-concept studies that were only performed in cells.

关键词： Photodynamic therapy Nanoparticle Tumor-targeting Drug delivery Tissue penetration

Multi-phase separation in mitochondrial nucleoids and eukaryotic nuclei

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Biophysics Reports 2023年第3期9卷 113-119页

作者： Qi Long Yanshuang Zhou Jingyi Guo Hao Wu Xingguo Liu CAS Key Laboratory of Regenerative Biology Joint School of Life Sciences The Sixth Affiliated Hospital of Guangzhou Medical University Qingyuan People's Hospital Guangzhou Medical University Guangzhou Institutes of biomedicine and Health Chinese Academy of Sciences Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine China-New Zealand Joint Laboratory on Biomedicine and Health CUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative Medicine Institute for Stem Cell and Regeneration Institute for Stem Cell and Regeneration Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Centre for Regenerative Medicine and Health Hong Kong Institute of Science & Innovation Chinese Academy of Sciences

In mammalian cells, besides nuclei, mitochondria are the only semi-autonomous organelles possessing own DNA organized in the form of nucleoids. While eukaryotic nuclear DNA compaction, chromatin compartmentalization and transcription are regulated by phase separation, our recent work proposed a model of mitochondrial nucleoid self-assembly and transcriptional regulation by multi-phase separation. Herein, we summarized the phase separation both in the nucleus and mitochondrial nucleoids,and did a comparison of the organization and activity regulating, which would provide new insight into the understanding of both architecture and genetics of nucleus and mitochondrial nucleoids.

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