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Accurate construction of cell membrane biomimetic graphene nanodecoys via purposeful surface engineering to improve screening efficiency of active components of traditional Chinese medicine

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Acta Pharmaceutica Sinica B 2022年第1期12卷 394-405页

作者： Qi Hu Lanlan Jia Xiaolin Zhang Aihong Zhu Sicen Wang Xiaoyu Xie School of Pharmacy Health Science CenterXi’an Jiaotong UniversityXi'an 710061China shaanxi engineering research center of cardiovascular drugs screening&analysis Xi'an 710061China

Biomimetic nanoengineering presents great potential in biomedical research by integrating cell membrane(CM) with functional nanoparticles. However, preparation of CM biomimetic nanomaterials for custom applications that can avoid the aggregation of nanocarriers while maintaining the biological activity of CM remains a challenge. Herein, a high-performance CM biomimetic graphene nanodecoy was fabricated via purposeful surface engineering, where polyethylene glycol(PEG) was used to modifying magnetic graphene oxide(MGO) to improve its stability in physiological solution, so as to improve the screening efficiency to active components of traditional Chinese medicine(TCM). With this strategy, the constructed PEGylated MGO(PMGO) could keep stable at least 10 days, thus improving the CM coating efficiency. Meanwhile, by taking advantage of the inherent ability of He La cell membrane(HM) to interact with specific ligands, HM-camouflaged PMGO showed satisfied adsorption capacity(116.2 mg/g) and selectivity. Finally, three potential active components, byakangelicol, imperatorin,and isoimperatorin, were screened from Angelica dahurica, whose potential antiproliferative activity were further validated by pharmacological studies. These results demonstrated that the purposeful surfaceengineering is a promising strategy for the design of efficient CM biomimetic nanomaterials, which will promote the development of active components screening in TCM.

关键词： Cell membrane Biomimetic nanoengineering Purposeful surface engineering Graphene oxide Dispersity Active components screening Traditional Chinese medicine PEGylation

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Biointerface engineering of self-protective bionic nanomissiles for targeted synergistic chemotherapy

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Chinese Chemical Letters 2023年第4期34卷 116-121页

作者： Xueyan Zhen Linhao Li Lanlan Jia Aihong Zhu Yixuan Yang Sicen Wang Xiaoyu Xie School of Pharmacy Health Science CenterXi’an Jiaotong UniversityXi’an 710061China shaanxi engineering research center of cardiovascular drugs screening&analysis Xi’an 710061China

Erythrocyte membrane(EM)-camouflaged chemotherapeutic delivery nanovehicles hold promise for solid tumor therapy because of their excellent biostability and biocompatibility. However, it is accompanied with insufficient targeting effect and deficient pharmacokinetic behavior due to the lack of a regulated biointerface to navigate and overcome biological transportation obstacles in solid tumor ***, an anti-epidermal growth factor receptor(EGFR) aptamer(EApt) modified and EM-cloaked chemotherapeutic nanomissile delivery system was constructed. The anchored-EApt acting as a specific EGFR suppressor promotes to inhibit the overexpression of EGFR and initiate the cell apoptosis. Importantly, the resulting PLGA-DOX@EM-EApt orchestrated the bioactivity of each component and provided synergistic cell apoptosis and antitumor effects by precisely suppressing EGFR expression levels and delivering DOX. The in vitro and in vivo experimental results confirmed that the immune escape and active targeting behaviors of PLGA-DOX@EM-EApt could significantly promote its drug retention and tumor inhibition abilities. Our findings propose a novel strategy using the biointerface functionalization technique, demonstrating a promising therapeutic platform via a biomimetic drug delivery system for precise solid tumor recognition and synergistic therapy.

关键词： Aptamer Self-protective Biointerface Targeted drug delivery Synergistic chemotherapy

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Precise assembly of inside-out cell membrane camouflaged nanoparticles via bioorthogonal reactions for improving drug leads capturing

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Acta Pharmaceutica Sinica B 2023年第2期13卷 852-862页

作者： Xiaolin Zhang Xueyan Zhen Yixuan Yang Quan Feng Wanqing Yuan Xiaoyu Xie School of Pharmacy Health Science CenterXi'an Jiaotong UniversityXi'an 710061China shaanxi engineering research center of cardiovascular drugs screening&analysis Xi'an 710061China

Cell membrane camouflaged nanoparticles have been widely used in the field of drug leads discovery attribute to their unique biointerface targeting ***,random orientation of cell membrane coating does not guarantee effective and appropriate binding of drugs to specific sites,especially when applied to intracellular regions of transmembrane *** reactions have been rapidly developed as a specific and reliable method for cell membrane functionalization without disturbing living ***,inside-out cell membrane camouflaged magnetic nanoparticles(IOCMMNPs)were accurately constructed via bioorthogonal reactions to screen small molecule inhibitors targeting intracellular tyrosine kinase domain of vascular endothelial growth factor *** functionalized cell membrane acted as a platform for specific covalently coupling with alkynyl functionalized magnetic Fe_(3)O_(4)nanoparticles to prepare *** inside-out orientation of cell membrane was successfully verified by immunogold staining and sialic acid quantification ***,two compounds,senkyunolide A and ligustilidel,were successfully captured,and their potential antiproliferative activities were further testified by pharmacological *** is anticipated that the proposed inside-out cell membrane coating strategy endows tremendous versatility for engineering cell membrane camouflaged nanoparticles and promotes the development of drug leads discovery platforms.

关键词： Cell membrane camouflaged nanoparticles Inside-out cell membrane coating Bioorthogonal reactions Drug leads discovery Traditional Chinese medicine Magnetic nanoparticles Precise assembly Alkynyl functionalization

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Recent advances in screening active components from natural products based on bioaffinity techniques

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Acta Pharmaceutica Sinica B 2020年第10期10卷 1800-1813页

作者： Xiaofang Hou Meng Sun Tao Bao Xiaoyu Xie Fen Wei Sicen Wang School of Pharmacy Health Science CenterXi’an Jiaotong UniversityXi’an 710061China College of Pharmacy Shaanxi University of Chinese MedicineXi’an 712046China shaanxi engineering research center of cardiovascular drugs screening&analysis Xi’an 710061China

Natural products have provided numerous lead compounds for drug ***,the traditional analytical methods cannot detect most of these active components,especially at their usual low concentrations,from complex natural ***,we reviewed the recent technological advances(2015-2019)related to the separation and screening bioactive components from natural resources,especially the emerging screening methods based on the bioaffinity techniques,including biological chromatography,affinity electrophoresis,affinity mass spectroscopy,and the latest magnetic and optical *** screening methods are uniquely advanced compared to other traditional methods,and they can fish out the active components from complex natural products because of the affinity between target and components,without tedious separation ***,these new tools can reduce the time and cost of the drug discovery process and accelerate the development of more effective and better-targeted therapeutic agents.

关键词： screening Active components Natural products Bioaffinity techniques

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Study on screening potential allergenic proteins from infant milk powders based on human mast cell membrane chromatography and histamine release assays

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Journal of Pharmaceutical analysis 2019年第1期9卷 55-61页

作者： Ping Zhang Yingdi Shi Xiaoshuang He Wei Sun Yanni Lv Xiaofang Hou School of Pharmacy Xi'an Jiaotong University Linyi Institute for Food and Drug Control shaanxi engineering research center of cardiovascular drugs screening & analysis

Cow's milk allergy is mainly observed in infants and young children. Most allergic reactions affect the skin, followed by the gastrointestinal and respiratory systems. Conventional diagnosis is based on positive allergy studies and evaluation of parameters including IgE and IgG1 levels, acute allergic skin response and anaphylactic shock reactions. We developed a cell membrane chromatographic(CMC)method based on human mast cells(HMC-1) for screening potential allergens in infant formula milk powders(IFMP). HMC-1 cell membranes were extracted and mixed with silica to prepare cell membrane chromatography columns(10 mm ? 2 mm i.d., 5 mm). Under the conditions of 0.2 mL/min flow rate and214 nm detection wavelength, human breast milk showed no retention. However, IFMP showed clear retention. The retained fractions were collected and analyzed through matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS). Four major milk proteins, i.e., α-casein, β-casein, α-lactalbumin, and β-lactoglobulin A, were identified. Furthermore, these proteins and β-lactoglobulin B showed clear retention on HMC-1/CMC columns. To test the degranulation effects of the five proteins, histamine and β-hexosaminidase release assays were carried out. All five proteins induced HMC-1 cells to release histamine and β-hexosaminidase. Also, we established a reversed phase liquid chromatographic(RPLC) method for the determination of the five proteins in IFMP and the results showed that 90% proteins in IFMP were α-casein and β-casein. We concluded that cow's milk proteins may be potential allergens and caseins cause more β-casein allergic risk than other proteins. This conclusion was consistent with other studies.

关键词： Allergenic proteins Cell membrane chromatography Milk powders

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Effective extraction of fluoroquinolones from water using facile modified plant fibers

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Journal of Pharmaceutical analysis 2022年第5期12卷 791-800页

作者： Nan Zhang Yan Gao Kangjia Sheng Wanghui Jing Xianliang Xu Tao Bao Sicen Wang School of Pharmacy Xi'an Jiaotong University Health Science CenterXi'an710061China Institute of Chinese Medical Sciences State Key Laboratory of Quality Research in Chinese MedicineUniversity of MacaoMacao999078China shaanxi engineering research center of cardiovascular drugs screening&analysis Xi'an710061China

In this study,ecofriendly and economic carboxy-terminated plant fibers(PFs)were used as adsorbents for the effective in-syringe solid phase extraction(IS-SPE)of fluoroquinolone(FQ)residues from *** on the thermal esterification and etherification reaction of cellulose hydroxy with citric acid(CA)and sodium chloroacetate in aqueous solutions,carboxy groups grafted onto cotton,cattail,and corncob fibers were *** with carboxy-terminated corncob and cotton,CA-modified cattail with more carboxy groups showed excellent adsorption capacity for *** modified cattail fibers were reproducible and reusable with relative standard deviations of 3.2%-4.2% within 10 cycles of adsorptiondesorption.A good extraction efficiency of 71.3%-80.9% was achieved after optimizing the extraction *** on carboxylated cattail,IS-SPE coupled with ultra-performance liquid chromatography with a photodiode array detector was conducted to analyze FQs in environmental water *** sensitivity with limit of detections of 0.08-0.25 mg/L and good accuracy with recoveries of 83.8%-111.7% were ***,the simple and environment-friendly modified waste PFs have potential applications in the effective extraction and detection of FQs in natural waters.

关键词： Fluoroquinolones Cattail fiber Carboxylation modification In-syringe solid phase extraction

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Application of microfluidic chip technology in pharmaceutical analysis:A review

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Journal of Pharmaceutical analysis 2019年第4期9卷 238-247页

作者： Ping Cui Sicen Wang School of Pharmacy Xi'an Jiaotong University Health Science Center#76 Yanta West Road Xi'an 710061 China shaanxi engineering research center of cardiovascular drugs screening & analysis Xi’an 710061 China

The development of pharmaceutical analytical methods represents one of the most significant aspects of drug development. Recent advances in microfabrication and microfluidics could provide new approaches for drug analysis, including drug screening, active testing and the study of metabolism. Microfluidic chip technologies, such as lab-on-a-chip technology, three-dimensional (3D) cell culture, organs-on-chip and droplet techniques, have all been developed rapidly. Microfluidic chips coupled with various kinds of detection techniques are suitable for the high-throughput screening, detection and mechanistic study of drugs. This review highlights the latest (2010–2018) microfluidic technology for drug analysis and discusses the potential future development in this field.

关键词： Microfluidic chip Pharmaceutical analysis Application research

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Kunxian Capsule Extract Inhibits Angiogenesis in Zebrafish Embryos via PI3K/AKT-MAPK-VEGF Pathway

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Chinese Journal of Integrative Medicine 2023年第2期29卷 137-145页

作者： MA Rui-jiao Maharajan Kannan XIA Qing ZHANG Shan-shan TU Peng-fei LIU Ke-chun ZHANG Yun Biology Institute Qilu University of Technology(Shandong Academy of Sciences)Jinan 250103China engineering research center of Zebrafish Models for Human Diseases and Drug screening of Shandong Province Jinan 250103China State Key Laboratory of Natural and Biomimetic drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Objective: To investigate the anti-angiogenic activity of Kunxian Capsule(KX) extract and explore the underlying molecular mechanism using zebrafish. Methods: The KX extract was prepared with 5.0 g in 100 mL of 40% methanol followed by ultrasonication and freeze drying. Freeze dried KX extract of 10.00 mg was used as test stock solution. Triptolide and icariin, the key bioactive compounds of KX were analyzed using ultra-high performance liquid chromatography. The transgenic zebrafish Tg(flk1:GFP) embryos were dechorionated at 20-h post fertilization(hpf) and treated with PTK 787, and 3.5, 7, 14 and 21 μg/m L of KX extract, *** 24-h post exposure(hpe), mortality and malformation(%), intersegmental vessels(ISV) formation, and m RNA expression level of angiogenic pathway genes including phosphoinositide 3-kinase(PI3K), protein kinase B(AKT),extracellular signal-regulated kinases(ERKs), mitogen-activated protein kinase(MAPK), vascular endothelial growth factor(VEGF) and fibroblast growth factor(FGF-2) were determined. Further, the embryos at 72 hpf were treated with KX extract to observe the development of sub-intestinal vein(SIV) after 24 hpe. Results: The chromatographic analysis of test stock solution of KX extract showed that triptolide and icariin was found as 0.089 mg/g and 48.74 mg/g, respectively, which met the requirements of the national drug standards. In zebrafish larvae experiment, KX extract significantly inhibited the ISV(Panalysis showed that KX extract could significantly suppress the expressions of PI3K and AKT,thereby inhibiting the m RNA levels of ERKs and MAPK. Moreover, the downstream signaling cascade affected the expression of VEGF and its receptors(VEGFR and VEGFR-2). FGF-2, a strong angiogenic factor, was also downregulated by KX treatment in zebrafish larvae. Conclusion: KX extract exhibited anti-angiogenic effects in zebrafish embryos by regulating PI3K/AKT-MAPK-VE

关键词： angiogenesis rheumatoid arthritis synovial inflammation osteoporosis Chinese medicine

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Bimetallic nanoparticles as cascade sensitizing amplifiers for low-dose and robust cancer radio-immunotherapy

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1787-1800页

作者： Yupeng Wang Lina Wang Tao Li Min Ouyang Hejian Xiong Dongfang Zhou Department of Ultrasonic Diagnosis Zhujiang HospitalKey Laboratory of Mental Health of the Ministry of EducationNMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Testing and analysis center Hebei Normal UniversityShijiazhuang 050024China Department of Mechanical engineering The University of Texas at DallasRichardsonTX 75080USA

Radiotherapy(RT)is one of the most feasible and routinely used therapeutic modalities for treating malignant *** particular,immune responses triggered by RT,known as radio-immunotherapy,can partially inhibit the growth of distantly spreading tumors and recurrent ***-ever,the safety and efficacy of radio-immunotherapy is impeded by the radio-resistance and poor immu-nogenicity of ***,we report oxaliplatin(IV)-iron bimetallic nanoparticles(OXA/Fe NPs)as cascade sensitizing amplifiers for low-dose and robust *** OXA/Fe NPs exhibit tumor-specific accumulation and activation of OXA(I)and Fe^(2+)in response to the reductive and acidic microenvironment within tumor *** cascade reactions of the released metallic drugs can sensitize RT by inducing DNA damage,increasing ROS and O_(2) levels,and amplifying the immunogenic cell death(ICD)effect after RT to facilitate potent immune *** a result,OXA/Fe NPs-based low-dose RT triggered a robust immune response and inhibited the distant and metastatic tumors effectively by a strong abscopal ***,a long-term immunological memory effect to protect mice from tumor rechal-lenging is ***,the bimetallic NPs-based cascade sensitizing amplifier system offers an effi-cient radio-immunotherapy regimen that addresses the key challenges.

关键词： Bimetallic nanoparticles Radio-immunotherapy Cascade sensitizing amplifier,Oxaliplatin Fenton-typeHaber-Weiss reaction Radiosensitization Immunogenic cell death Radio-resistance

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In situ visualization of the cellular uptake and sub-cellular distribution of mussel oligosaccharides

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Journal of Pharmaceutical analysis 2024年第6期14卷 840-850页

作者： Zhenjie Yu Huarong Shao Xintian Shao Linyan Yu Yanan Gao Youxiao Ren Fei Liu Caicai Meng Peixue Ling Qixin Chen Key Laboratory for Biotechnology drugs of National Health Commission School of Pharmaceutical Sciences&Institute of Materia MedicaMedical Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinan250117China Key Laboratory of Biopharmaceuticals Engineering Laboratory of Polysaccharide DrugsNational-Local Joint Engineering Laboratory of Polysaccharide DrugsShandong Academy of Pharmaceutical ScienceJinan250101China Shenzhen research Institute of Xiamen University ShenzhenGuangdong518057China School of Life Sciences Medical Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinan250117China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and Faculty of EngineeringNational University of SingaporeSingapore119074Singapore School of Pharmaceutical Sciences Shandong UniversityJinan250101China

Unlike chemosynthetic drugs designed for specific molecular and disease targets,active small-molecule natural products typically have a wide range of bioactivities and multiple targets,necessitating extensive screening and *** address this issue,we propose a strategy for the direct in situ microdynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of *** a proof-of-concept,we investigated the behavior of mussel oligosaccharide(MOS-1)by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured *** recorded the entire dynamic process of the localization of fluorescein isothiocyanate(FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the ***,lysosomes containing FITC-MOS-1 actively recruited lipid droplets,leading to fusion events and increased cellular lipid *** drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related ***,in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E(ApoE)^(-/-)mice,MOS-1 significantly promoted triglyceride degradation,reduced lipid droplet accumulation,lowered serum triglyceride levels,and mitigated liver damage and ***,our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase,as this methodology contributes to the rapid identification of drug ***,this methodology is significant for the screening and development of selective small-molecule drugs,and is expected to expedite the identification of candidate molecules with medicinal effects.

关键词： Cellular imaging Fluorescence labeling Mussel oligosaccharide Lipid metabolism

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