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Macrophage-evading and tumor-specific apoptosis inducing nanoparticles for targeted cancer therapy

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Acta Pharmaceutica Sinica B 2023年第1期13卷 327-343页

作者： Zimo Liu Xuefei Zhou Qi Li Youqing Shen Tianhua Zhou Xiangrui Liu department of Pharmacology and department of Gastroenterology of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China College of chemical and Biological Engineering Zhejiang UniversityHangzhou 310027China International Institutes of Medicine The Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwu 322000China Cancer Center Zhejiang UniversityHangzhou 310058China department of Cell Biology School of MedicineZhejiang UniversityHangzhou 310058China

Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications.However,administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system(MPS).In this study,we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues.The fabricated nanoparticles(TM-CQ/NPs)were coated with fibroblast cell membrane expressing tumor necrosis factor(TNF)-related apoptosis inducing ligand(TRAIL).Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages,but increased the nanoparticle uptake in tumor cells.Importantly,this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death receptors.Meanwhile,the encapsulated chloroquine(CQ)further suppressed the uptake of nanoparticles by macrophages,and synergized with TRAIL to induce tumor cell apoptosis.The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer therapy.Together,our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.

关键词： TRAIL Fibroblast Nanoparticles Mononuclear phagocyte system Membrane coating Chloroquine Cancer therapy Drug delivery

A flexible solid polymer electrolyte enabled with lithiated zeolite for high performance lithium battery

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Nano Research 2023年第7期16卷 9443-9452页

作者： Zhiyu Ding Qiming Tang Qi Zhang Penghui Yao Xingjun Liu Junwei Wu Shenzhen Key Laboratory of Advanced Materials Department of Materials Science and EngineeringHarbin Institute of Technology(Shenzhen)Shenzhen 518055China Maryland Energy Innovation Institute University of MarylandCollege ParkMD 20742USA department of chemical and Metallurgical Engineering Aalto UniversityKemistintie 1Aalto FI-00076Finland

Solid-state lithium batteries using composite polymer electrolytes(CPEs)have attracted much attention owing to their higher safety compared to liquid electrolytes and flexibility compared to ceramic electrolytes.However,their unsatisfactory lithium-ion conductivity still limits their development.Herein,a high ion conductive CPE with multiple continuous lithium pathways is designed.This new electrolyte consists of poly(vinylidene fluorideco-hexafluoropropylene)(PVDF-HFP)and lithiated X type zeolite(Li-X),which possesses a high ionic conductivity(1.98×10^(-4)S/cm),high lithium transference number(t_(Li^(+))=0.55),wide electrochemical window(4.7 V),and excellent stability against the lithium anode.Density functional theory(DFT)calculation confirms that the Lewis acid sites in zeolite can graft with N,N-dimethylformamide(DMF)and PVDF-HFP chains,resulting in decreased crystallinity of polymer and providing rapid Li+transmission channels.When used in a full cell,the solid Li|Li-X-3%|LiFePO_(4) cell displays excellent cycling stability and rate performance at room temperature and 60℃.Furthermore,pouch cells with the Li-X-3%electrolyte exhibit brilliant safety under extreme conditions,such as folding and cutting.Thus,this proposed zeolite-PVDF-HFP CPE represents a promising potential in the application of making a safer,higher performing,and flexible solid-state lithium battery.

关键词： solid-state lithium batteries composite polymer electrolytes zeolite poly(vinylidene fluorideco-hexafluoropropylene)(PVDF-HFP) flexible

Cardioprotective effects of Pinus eldarica bark extract on adrenaline-induced myocardial infarction in rats

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Asian Pacific Journal of Tropical Biomedicine 2023年第4期13卷 148-155页

作者： Leila Safaeian Zahra Haghighatian Behzad Zolfaghari Mahdi Amindeldar department of Pharmacology and Toxicology Isfahan Pharmaceutical Sciences Research CenterSchool of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical SciencesIsfahanIran department of pathology School of MedicineLorestan University of Medical SciencesKhorramabadIran department of Pharmacognosy School of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical SciencesIsfahanIran

Objective:To investigate the effect of Pinus eldarica bark extract on adrenaline-induced myocardial infarction.Methods:Hydroalcoholic extract was prepared using maceration method and its total phenolic content was determined using the Folin-ciocalteu method.Pretreatment was done by oral administration of 100,200,and 400 mg/kg Pinus eldarica bark extract for 16 days in male Wistar rats.Injection of adrenaline(2 mg/kg,s.c.)was performed on the 15th and 16th days for induction of myocardial infarction.LeadⅡEEG was recorded.Serum cardiac marker enzymes and antioxidative parameters were evaluated and a histopathological examination of heart tissues was performed.Results:Pretreatment with Pinus eldarica bark extract especially at its high doses significantly lowered the ST-segment elevation,improved heart rate,and decreased RR interval in ECG pattern of rats with adrenaline-induced myocardial infarction.It declined serum markers of heart damage including aspartate aminotransferase,lactate dehydrogenase,and creatine phosphokinase-MB,and also decreased lipid peroxidation marker,and heart weight while raising total antioxidant capacity and considerably improved histopathological alterations of the heart induced by adrenaline.Conclusions:Pinus eldarica bark extract shows beneficial cardioprotective and antioxidant effects against adrenaline-induced myocardial infarction.It can be further explored as a potential treatment for myocardial infarction.

关键词： Adrenaline Antioxidant Lipid peroxidation Myocardial infarction Pinus eldarica

Recovery of Aniline from Wastewater by Nitrobenzene Extraction Enhanced with Salting-Out Effect

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Biomedical and Environmental Sciences 2010年第3期23卷 208-212页

作者： CHANG-HAI LI department of chemical Engineering Binzhou UniversityBinzhou 256603ShangdongChina School of chemical Engineering Changchun University of TechnologyChangchun 130012JilinChina

Objective Nitrobenzene extraction enhanced by salting-out effect was employed to recover aniline from wastewater at 25 ℃. Method Batchwise experiments were conducted to elucidate the influence of various operating variables on the extracting performance, including acidity of wastewater, initial aniline concentration, ratios of solvent to wastewater, extraction stages, concentrations and different types of inorganic salts, such as NaCl, KCI, Na2SO4, CaCl2 and K29O4. Results Nitrobenzene with a concentration of 20% and a pH value of 9.1 at the temperature of 25 ℃ together with NaCl of a concentration of 14 wt.% realized nearly 100% aniline recovery at the fifth stage of wastewater treatment. Conclusions High pH values and volume ratios of nitrobenzene/wastewater are more suitable for recovery of aniline. In addition, recovery of aniline is significantly elevated with increase of the concentration of salts, whose promoting effects are in the following order: NaCI〉Na2SO4〉K2SO4〉CaC12〉KCI on the weight basis of wastewater. Furthermore, aniline in wastewater can be almost completely recovered by five-stage sequential nitrobenzene extraction, which is promoted continuously by the salting-out effect.

关键词： Aniline Nitrobenzene Extraction Salting-out

PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain

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Genes & Diseases 2023年第4期10卷 1702-1713页

作者： Yamu Li Zhonghua Liu Yiqing Zhao Jie Yang Tsan Sam Xiao Ronald A.Conlon Zhenghe Wang department of Genetics and Genome Sciences Case Western Reserve UniversityClevelandOH 44106USA Case Comprehensive Cancer Center Case Western Reserve UniversityClevelandOH 44106USA department of pathology Case Western Reserve UniversityClevelandOH 44106USA department of Physiology and Biophysics Case Western Reserve UniversityClevelandOH 44106USA department of Integrative Structural and Computational Biology The Scripps Research Institute10550 North Torrey Pines RdTRY-21La JollaCA 92037USA.

How PD-L1 expression is regulated in cancer is poorly understood.Here,we report that the ATP-binding activity of ERBB3 pseudokinase regulates PD-L1 gene expression in colorectal cancers(CRCs).ERBB3 is one of the four members of the EGF receptor family,all with protein tyrosine kinase domains.ERBB3 is a pseudokinase with a high binding affin-ity to ATP.We showed that ERBB3 ATP-binding inactivation mutant reduces tumorigenicity in genetically engineered mouse models and impairs xenograft tumor growth of CRC cell lines.The ERBB3 ATP-binding mutant cells dramatically reduce IFN-g-induced PD-L1 expres-sion.Mechanistically,ERBB3 regulates IFN-g-induced PD-L1 expression through the IRS1-PI3K-PDK1-RSK-CREB signaling axis.CREB is the transcription factor that regulates PD-L1 gene expression in CRC cells.Knockin of a tumor-derived ERBB3 mutation located in the ki-nase domain sensitizes mouse colon cancers to anti-PD1 antibody therapy,suggesting that ERBB3 mutations could be predictive biomarkers for tumors amenable to immune check-point therapy.

关键词： Colon cancer ERBB3 Immunotherapy PD-L1 Pseudokinase

One-Dimensional Magnetic FeCoNi Alloy Toward Low-Frequency Electromagnetic Wave Absorption

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Nano-Micro Letters 2022年第10期14卷 260-272页

作者： Bintong Yang Jiefeng Fang Chunyang Xu Hui Cao Ruixuan Zhang Biao Zhao Mengqiu Huang Xiangyu Wang Hualiang Lv Renchao Che Laboratory of Advanced Materials Shanghai Key Lab of Molecular Catalysis and Innovative MaterialsDepartment of Materials ScienceFudan UniversityShanghai 200438People’s Republic of China Willian G.Lowrie department of chemical and Biomolecular Engineering The Ohio State UniversityColumbusOH 43210USA Zhejiang Laboratory Joint-Research Center for Computational MaterialsHangzhou 311100People’s Republic of China

Rational designing of one-dimensional(1D)magnetic alloy to facilitate electromagnetic(EM)wave attenuation capability in low-frequency(2-6 GHz)microwave absorption field is highly desired but remains a significant challenge.In this study,a composite EM wave absorber made of a FeCoNi medium-entropy alloy embedded in a 1D carbon matrix framework is rationally designed through an improved electrospinning method.The 1D-shaped FeCoNi alloy embedded composite demonstrates the high-density and continuous magnetic network using off-axis electronic holography technique,indicating the excellent magnetic loss ability under an external EM field.Then,the in-depth analysis shows that many factors,including 1D anisotropy and intrinsic physical features of the magnetic medium-entropy alloy,primarily contribute to the enhanced EM wave absorption performance.Therefore,the fabricated EM wave absorber shows an increasing effective absorption band of 1.3 GHz in the low-frequency electromagnetic field at an ultrathin thickness of 2 mm.Thus,this study opens up a new method for the design and preparation of high-performance 1D magnetic EM absorbers.

关键词： Medium-entropy magnetic alloy One-dimension Off-axis electronic holography technique Improved electrospinning Lower-frequency electromagnetic wave absorption

Evaluation of quality of clinical management of neuroendocrine tumors

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Cancer Innovation 2022年第4期1卷 305-315页

作者： Hannah Bloemen Kristien Kneepkens Karen Deraedt Anna Ivanova Gregory Sergeant Jeroen Mebis Kurt Van der Speeten department of Medicine Faculty of Medicine and Life Sciences(LCRC)Hasselt UniversityDiepenbeekBelgium department of pathology and department Future Health Ziekenhuis Oost-LimburgGenkBelgium department of Abdominal Surgery and department Jessa&Science Jessa HospitalHasseltBelgium department of Medical Oncology and department Jessa&Science Jessa HospitalHasseltBelgium department of Surgical Oncology and department Future Health Ziekenhuis Oost-LimburgGenkBelgium

Background:Neuroendocrine tumors(NETs)are a group of biologically and clinically heterogeneous neoplasms predominantly found in the gastrointestinal and bronchopulmonary tractus.Despite a rising incidence,implementation of evidence-based standardized care for this heterogenous group remains challenging.The European Neuroendocrine Tumor Society regularly reviews guidelines regarding diagnostic and treatment strategies for NETs.The aim of this study is to shed light on the care of patients with a NET in Belgian Limburg,to provide data as a basis for future studies and to check whether data and results are according to consensus guidelines and outcomes described in literature.Methods:Our study concerned a detailed observational data collection of two large Belgian hospitals(Jessa Hospital Hasselt and Hospital Oost-Limburg Genk)with special interest in patient profile,quality of pathology reports,use of diagnostic imaging,and overall survival.Data on 188 patients were assembled between January 2010 and December 2014 with follow-up until June 2016(median follow-up:33.6 months).Results:Fifty percent of patients were male.NETs were located mainly in the digestive tract(63.8%)and lung(20.2%).Appendiceal NETs were diagnosed at a significantly younger age than other tumors(41.3 vs.64.0 years).Overall,a mean pathology report quality score of 3.0/5 was observed with the highest scores for small bowel NETs.Diagnostic and nuclear imaging was performed in 74.5%and 29.8%of cases,respectively.Seventy-four percent of the population survived until the end of the observation period with highest survival rates for appendiceal and small bowel NETs.Conclusion:Overall,epidemiological results were comparable with findings in the literature.Gastrointestinal NETs met most of the requirements of qualitative pathology reporting and diagnostic imaging as listed in the European Neuroendocrine Tumor Society consensus guidelines.However,consensus with regard to bronchopulmonary NETs is still scarce and remains an objective for future research.Mo

关键词： neuroendocrine tumors epidemiology quality pathology report Ki67 overall survival guidelines

Development of a miniaturized 3D organoid culture platform for ultra-high-throughput screening

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Journal of Molecular Cell Biology 2020年第8期12卷 630-643页

作者： Yuhong Du Xingnan Li Qiankun Niu Xiulei Mo Min Qui Tingxuan Ma Calvin J.Kuo Haian Fu department of Pharmacology and chemical Biology and Emory chemical Biology Discovery Center Emory University School of MedicineAtlantaGAUSA department of Medicine Division of HematologyStanford University School of MedicineStanfordCAUSA

The recent advent of robust methods to grow human tissues as 3D organoids allows us to recapitulate the 3D architecture of tumors in an in vitro setting and offers a new orthogonal approach for drug discovery.However,organoid culturing with extracellular matrix to support 3D architecture has been challenging for high-throughput screening(HTS)-based drug discovery due to technical difficulties.Using genetically engineered human colon organoids as a model system,here we report our effort to miniaturize such 3D organoid culture with extracellular matrix support in high-density plates to enable HTS.We first established organoid culturing in a 384-well plate format and validated its application in a cell viability HTS assay by screening a 2036-compound library.We further miniaturized the 3D organoid culturing in a 1536-well ultra-HTS format and demonstrated its robust performance for large-scale primary compound screening.Our miniaturized organoid culturing method may be adapted to other types of organoids.By leveraging the power of 3D organoid culture in a high-density plate format,we provide a physiologically relevant screening platform to model tumors to accelerate organoid-based research and drug discovery.

关键词： human colon organoids KRAS^G12D 3D culture 384-well plate high-throughput screening(HTS) 1536-well plate ultra-HTS(uHTS)

Atomic-level correlation between the electrochemical performance of an oxygen-evolving catalyst and the effects of CeO_(2) functionalization

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Nano Research 2022年第4期15卷 2994-3000页

作者： Yanyan Li Wen Luo Duojie Wu Qi Wang Jie Yin Pinxian Xi Yongquan Qu Meng Gu Xinyu Zhang Zhouguang Lu Zhiping Zheng School of Chemistry and chemical Engineering Harbin Institute of TechnologyHarbin 150001China department of Chemistry Guangdong Provincial Key Laboratory of Energy Materials for Electric PowerSouthern University of Science and TechnologyShenzhen 518055China Key Laboratory of Energy Conversion and Storage Technologies(Southern University of Science and Technology) Ministry of EducationShenzhen 518055China department of Materials Science and Engineering Shenzhen Key Laboratory of Interfacial Science and Engineering of MaterialsSouthern University of Science and TechnologyShenzhen 518055China department of Materials Science and Engineering Guangdong Provincial Key Laboratory of Energy Materials for Electric PowerSouthern University of Science and TechnologyShenzhen 518055China Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering Research Centre of Biomedical NanotechnologyLanzhou UniversityLanzhou 730000China School of chemical Engineering and Technology Center for Applied Chemical ResearchFrontier Institute of Science and TechnologyXi'an Jiaotong UniversityXi'an 710049China

Herein,we prepared a bimetallic layered double hydroxide(FeCo LDH)featuring a dandelion-like structure.Anchoring of CeO_(2)onto FeCo LDH produced interfaces between the functionalizing CeO_(2)and the parent LDH.Comparative electrochemical studies were carried out.Onset potential,overpotential,and Tafel slope point to the superior oxygen-evolving performance of CeO_(2)-FeCo LDH with respect to FeCo LDH,therefore,demonstrating the merits of CeO_(2)functionalization.The electronic structures of Fe,Co,and Ce were analyzed by X-ray photoelectron spectroscopy(XPS)and electron energy loss spectroscopy(EELS)from which the increase of Co^(3+)and the concurrent lowering of Ce^(4+)were established.With the use of CeO_(2)-FeCo LDH,accelerated formation at a sizably reduced potential of Co-OOH,one of the key intermediates preceding the release of O_(2)was observed by in situ Raman spectroscopy.We now have the atomic-level and location-specific evidence,the increase of the active Co^(3+)across the interface to correlate the enhanced catalytic performance with CeO_(2)functionalization.

关键词： CeO_(2)nanoparticles metal layered double hydroxides(LDHs) oxygen evolution reaction intermediate conversion