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The spectrum of building block conformers sustains the biophysical properties of clinically-oriented self-assembling protein nanoparticles

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science China Materials 2022年第6期65卷 1662-1670页

作者： Eric Voltà-Durán Julieta M sánchez Hèctor-López-Laguna Eloi Parladé laura sánchez-garcía Alejandro sánchez-Chardi Ario de Marco Ugutz Unzueta Esther Vázquez Antonio Villaverde Institut de Biotecnologia i de Biomedicina Universitat Autònoma de BarcelonaBellaterra 08193BarcelonaSpain Departament de Genètica i de Microbiologia Universitat Autònoma de BarcelonaBellaterra 08193BarcelonaSpain CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN) Bellaterra 08193BarcelonaSpain Instituto de Investigaciones Biológicas y Tecnológicas(IIBYT)(CONICET-Universidad Nacional de Córdoba) ICTA&Cátedra de Química BiológicaDepartamento de QuímicaFCEFyNUNC.Av.Velez Sarsfield 1611X 5016GCA CórdobaArgentina servei de Microscòpia Universitat Autònoma de BarcelonaBellaterra 08193BarcelonaSpain Departament de Biologia Evolutiva Ecologia i Ciències AmbientalsFacultat de BiologiaUniversitat de Barcelona08028 BarcelonaSpain Laboratory for Environmental and Life sciences University of Nova GoricaNova Gorica 5000Slovenia Biomedical Research Institute sant Pau(IIB sant Pau) Sant Antoni Ma Claret 16708025 BarcelonaSpain

Histidine-rich peptides confer self-assembling properties to recombinant proteins through the supramolecular coordination with divalent cations.This fact allows the cost-effective,large-scale generation of microscopic and macroscopic protein materials with intriguing biomedical properties.Among such materials,resulting from the simple bioproduction of protein building blocks,homomeric nanoparticles are of special value as multivalent interactors and drug carriers.Interestingly,we have here identified that the assembly of a given His-tagged protein might render distinguishable categories of self-assembling protein nanoparticles.This fact has been scrutinized through the nanobody-containing fusion proteins EM1-GFP-H6 and A3C8-GFP-H6,whose biosynthesis results in two distinguishable populations of building blocks.In one of them,the assembling and disassembling is controllable by cations.However,a second population immediately self-assembles upon purification through a non-regulatable pathway,rendering larger nanoparticles with specific biological properties.The structural analyses of both model proteins and nanoparticles revealed important conformational variability in the building blocks.This fact renders different structural and functional categories of the final soft materials resulting from the participation of energetically unstable intermediates in the oligomerization process.These data illustrate the complexity of the Hismediated protein assembling in recombinant proteins but they also offer clues for a better design and refinement of protein-based nanomedicines,which,resulting from biological fabrication,show an architectonic flexibility unusual among biomaterials.

关键词： recombinant proteins self-assembling protein materials nanoparticles biomaterials

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self-assembling protein nanocarrier for selective delivery of cytotoxic polypeptides to CXCR4^(+) head and neck squamous cell carcinoma tumors

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Acta Pharmaceutica sinica B 2022年第5期12卷 2578-2591页

作者： Elisa Rioja-Blanco Irene Arroyo-solera Patriciaálamo Isolda Casanova Alberto Gallardo Ugutz Unzueta Naroa serna laura sánchez-garcía Miquel Quer Antonio Villaverde Esther Vázquez Ramon Mangues Lorena Alba-Castellón Xavier León Institut d'InvestigacióBiomèdica sant Pau(IIB-sant Pau) Barcelona 08041Spain Institut de Recerca contra la Leucèmia Josep Carreras Barcelona 08025Spain CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)Madrid 28029Spain Department of Pathology Hospital de la Santa Creu i Sant PauBarcelona 08041Spain Institut de Biotecnologia i de Biomedicina Universitat Autònoma de BarcelonaBellaterra 08193Spain Departament de Genètica i de Microbiologia Universitat Autònoma de BarcelonaBellaterra 08193Spain Department of Otorhinolaryngology Hospital de la Santa Creu i Sant PauBarcelona 08041Spain

Loco-regional recurrences and distant metastases represent the main cause of head and neck squamous cell carcinoma(HNsCC) mortality. The overexpression of chemokine receptor 4(CXCR4) in HNsCC primary tumors associates with higher risk of developing loco-regional recurrences and distant metastases, thus making CXCR4 an ideal entry pathway for targeted drug delivery. In this context, our group has generated the self-assembling protein nanocarrier T22-GFP-H6, displaying multiple T22 peptidic ligands that specifically target CXCR4. This study aimed to validate T22-GFP-H6 as a suitable nanocarrier to selectively deliver cytotoxic agents to CXCR4^(+)tumors in a HNsCC model. Here we demonstrate that T22-GFP-H6 selectively internalizes in CXCR4^(+)HNsCC cells, achieving a high accumulation in CXCR4^(+)tumors in vivo, while showing negligible nanocarrier distribution in non-tumor bearing organs. Moreover, this T22-empowered nanocarrier can incorporate bacterial toxin domains to generate therapeutic nanotoxins that induce cell death in CXCR4-overexpressing tumors in the absence of histological alterations in normal organs. Altogether, these results show the potential use of this T22-empowered nanocarrier platform to incorporate polypeptidic domains of choice to selectively eliminate CXCR4^(+)cells in HNsCC. Remarkably, to our knowledge, this is the first study testing targeted proteinonly nanoparticles in this cancer type, which may represent a novel treatment approach for HNsCC patients.

关键词： Targeted drug delivery Protein nanoparticles CXCR4 receptor HNsCC Cell targeting Recombinant proteins Nanotoxins Cancer therapy

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重组氯毒素构建细胞靶向的活性纳米颗粒(英文)

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science China Materials 2019年第6期62卷 892-898页

作者： Raquel Díaz laura sánchez-garcía Naroa serna Alejandro sánchez-Chardi Olivia Cano-Garrido Julieta M.sánchez Ugutz Unzueta Esther Vazquez Antonio Villaverde Institut de Biotecnologia i de Biomedicina Universitat Autònoma de Barcelona Departament de Genètica i de Microbiologia Universitat Autònoma de Barcelona CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN) servei de Microscòpia Universitat Autònoma de Barcelona Biomedical Research Institute sant Pau(IIB-sant Pau)and Josep Carreras Research Institute Hospital de la Santa Creu i Sant Pau Universidad Nacional de Córdoba Facultad de Ciencias ExactasFísicas y Naturales.ICTA and Departamento de QuímicaCátedra de Química Biológica.Córdoba.Argentina.CONICETInstituto de Investigaciones Biológicas y Tecnológicas(IIBYT)

功能性蛋白质在纳米尺度的可控寡聚化提供了通过重组DNA技术来设计和生产改良材料和药物的可能性.氯毒素(CTX),作为一种重组的蝎毒素,由于其优先结合癌细胞的能力而引起人们的兴趣.本研究将氯毒素设计并自组装为12 nm的常规纳米颗粒,这... 详细信息

功能性蛋白质在纳米尺度的可控寡聚化提供了通过重组DNA技术来设计和生产改良材料和药物的可能性.氯毒素(CTX),作为一种重组的蝎毒素,由于其优先结合癌细胞的能力而引起人们的兴趣.本研究将氯毒素设计并自组装为12 nm的常规纳米颗粒,这些纳米颗粒可穿透具有和天然毒素相同受体特异性的培养细胞.这些生物相容且可生物降解的材料,表现出与同时作为载体和治疗剂的重组毒素相应的温和但仍然显著的细胞毒活性,有希望成为用于细胞靶向治疗胶质瘤的药物载体.此外,对CTX侧区域的修改可有效影响纳米颗粒的性能,说明基于CTX的构建体可通过常规基因工程来调节其多重功能性.

关键词：重组DNA技术细胞毒活性纳米颗粒蝎毒素癌细胞可生物降解氯药物载体

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Biomass gasification,catalytic technologies and energy integration for production of circular methanol:New horizons for industry decarbonisation

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Journal of Environmental sciences 2024年第6期140卷 306-318页

作者： Luis F.Bobadilla Lola Azancot Miriam González-Castañ Estela Ruíz-López laura Pastor-Pérez Francisco J.Durán-Olivencia Runping Ye Katie Chong Paula HBlanco-sánchez Zenthao Wu Tomás R.Reina JoséA.Odriozola Departamento de Química Inorgánica e Instituto de Ciencia de Materiales de sevilla Centro Mixto CSIC-Universidad de SevillaAvda.Américo Vespucio 49Sevilla 41092Spain Departamento de Ingeniería Universidad Loyola AndalucíaAvda.de Las Universidades s/nSevilla 41704Spain Key Laboratory of Jiangxi Province for Environment and Energy Catalysis School of Chemistry and Chemical EngineeringNanchang UniversityNanchang330031China Energy and Bioproducts Research Institute(EBRI) Aston UniversityBirminghamB47ETUnited Kingdom Department of Chemical and Process Engineering University of SurreyGuildfordGU27XHUnited Kingdom

The Intergovernmental Panel on Climate Change(IPCC)recognises the pivotal role of renewable energies in the future energy system and the achievement of the zero-emission target.The implementation of renewables should provide major opportunities and enable a more secure and decentralised energy supply system.Renewable fuels provide long-term solutions for the transport sector,particularly for applications where fuels with high energy density are required.In addition,it helps reducing the carbon footprint of these sectors in the long-term.Information on biomass characteristics feedstock is essential for scaling-up gasification from the laboratory to industrial-scale.This review deals with the transformation biogenic residues into a valuable bioenergy carrier like biomethanol as the liquid sunshine based on the combination of modified mature technologies such as gasification with other innovative solutions such as membranes and microchannel reactors.Tar abatement is a critical process in product gas upgrading since tars compromise downstream processes and equipment,for this,membrane technology for upgrading syngas quality is discussed in this paper.Microchannel reactor technology with the design of state-of-the-art multifunctional catalysts provides a path to develop decentralised biomethanol synthesis from biogenic residues.Finally,the development of a process chain for the production of(i)methanol as an intermediate energy carrier,(ii)electricity and(iii)heat for decentralised applications based on biomass feedstock flexible gasification,gas upgrading and methanol synthesis is analysed.

关键词： Biogenic residues Gasification Biomethanol Circular Economy Microreactors

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Long-term effects of gestational diabetes mellitus on the pancreas of female mouse offspring

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World Journal of Diabetes 2024年第4期15卷 758-768页

作者： Enriqueta Muñoz-Islas Edgar David santiago-sanMartin Eduardo Mendoza-sánchez Héctor Fabián Torres-Rodríguez laura Yanneth Ramírez-Quintanilla Christopher Michael Peters Juan Miguel Jiménez-Andrade Unidad Académica Multidisciplinaria Reynosa-Aztlán Universidad Autónoma de TamaulipasReynosa 88740TamaulipasMexico Department of Anesthesiology Wake Forest University School of MedicineWinston SalemNC 27101United States

BACKGROUND Prolonged fetal exposure to hyperglycemia may increase the risk of developing abnormal glucose metabolism and type-2 diabetes during childhood,adolescence,and adulthood;however,the mechanisms by which gestational diabetes mellitus(GDM)predisposes offspring to metabolic disorders remain unknown.AIM To quantify the nerve axons,macrophages,and vasculature in the pancreas from adult offspring born from mouse dams with GDM.METHODs GDM was induced by i.***.administration of streptozotocin(sTZ)in ICR mouse dams.At 12 wk old,fasting blood glucose levels were determined in offspring.At 15 wk old,female offspring born from dams with and without GDM were sacrificed and pancreata were processed for immunohistochemistry.We quantified the density of sensory[calcitonin gene-related peptide(CGRP)]and tyrosine hydroxylase(TH)axons,blood vessels(endomucin),and macro-phages(CD68)in the splenic pancreas using confocal microscopy.REsULTs Offspring mice born from sTZ-treated dams had similar body weight and blood glucose values compared to offspring born from vehicle-treated dams.However,the density of CGRP+and TH+axons,endomucin+blood vessels,and CD68+macrophages in the exocrine pancreas was significantly greater in offspring from mothers with GDM vs control offspring.Likewise,the microvasculature in the islets was significantly greater,but not the number of macrophages within the islets of offspring born from dams with GDM compared to control mice.CONCLUsION GDM induces neuronal,vascular,and inflammatory changes in the pancreas of adult progeny,which may partially explain the higher propensity for offspring of mothers with GDM to develop metabolic diseases.

关键词： Gestational diabetes mellitus Immunohistochemistry Confocal microscopy Pancreas Offspring

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Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering

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science China Materials 2020年第1期63卷 147-156页

作者： Eric Volta-Duran Olivia Cano-Garrido Naroa serna Hector Lopez-Laguna laura sanchez-garcia Mireia Pesarrodona Alejandro sanchez-Chardi Ramon Mangues Antonio Villaverde Esther Vazquez Ugutz Unzueta Institut de Biotecnologia i de Biomedicina Universitat Autònoma de BarcelonaBellaterra08193 BarcelonaSpain Departament de Genetica i de Microbiologia Universitat Autònoma de BarcelonaBellaterra08193 BarcelonaSpain CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)C/Monforte de Lemos 3-528029 MadridSpain Nanoligent sL Edifici EUREKAUniversitat Autonoma de BarcelonaBellaterra08193 BarcelonaSpain Institut dInvestigacions Biomèdiques sant Pau and Josep Carreras Research Institute Hospital de la Santa Creu i Sant Pau08041 BarcelonaSpain Departament de Biologia Evolutiva Ecologia i Ciencies AmbientalsFacultat de BiologiaUniversitat de BarcelonaAv.Diagonal 64308028 BarcelonaSpain Institute for Research in Biomedicine(IRB Barcelona) The Barcelona Institute of Science and Technology08028 BarcelonaSpain

Modular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize as supramolecular entities and to generate multifunctional protein materials. To explore this concept, we have repositioned functional segments in the modular protein T22-GFP-H6 and characterized the resulting alternative fusions. In T22-GFP-H6, the combination of T22 and H6 promotes selfassembling as regular nanoparticles and selective binding and internalization of this material in CXCR4-overexpressing tumor cells, making them appealing as vehicles for selective drug delivery. The results show that the pleiotropic activities are dramatically affected in module-swapped constructs, proving the need of a carboxy terminal positioning of H6 for protein self-assembling, and the accommodation of T22 at the amino terminus as a requisite for CXCR4^+ cell binding and internalization. Furthermore, the failure of self-assembling as regular oligomers reduces cellular penetrability of the fusions while keeping the specificity of the T22-CXCR4 interaction.All these data instruct how multifunctional nanoscale protein carriers can be designed for smart, protein-driven drug delivery, not only for the treatment of CXCR4^+ human neoplasias, but also for the development of anti-HIV drugs and other pathologies in which CXCR4 is a relevant homing marker.

关键词： nanoparticles protein materials recombinant proteins drug delivery self-assembling cancer cell targeting

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Electrifying Ba_(0.5)sr_(0.5)Co_(0.8)Fe_(0.2)O_(3-δ) for focalized heating in oxygen transport membranes

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Journal of Energy Chemistry 2024年第4期91卷 99-110页

作者： Marwan Laqdiem Julio garcía-Fayos laura Almar Alfonso J.Carrillo Álvaro Represa JoséM.López Nieto sonia Escolástico David Catalán-Martinez Jose M.serra Instituto de Tecnología Química(Universitat Politècnica de València–Consejo superior de Investigaciones Científicas) Av.Los Naranjos s/nE-46022 ValenciaSpain

Industry decarbonization requires the development of highly efficient and flexible technologies relying on renewable energy resources,especially biomass and solar/wind electricity.In the case of pure oxygen production,oxygen transport membranes(OTMs)appear as an alternative technology for the cryogenic distillation of air,the industrially-established process of producing oxygen.Moreover,OTMs could provide oxygen from different sources(air,water,CO_(2),etc.),and they are more flexible in adapting to current processes,producing oxygen at 700^(-1)000℃.Furthermore,OTMs can be integrated into catalytic membrane reactors,providing new pathways for different processes.The first part of this study was focused on electrification on a traditional OTM material(Ba_(0.5)sr_(0.5)Co_(0.8)Fe_(0.2)O_(3-δ)),imposing different electric currents/voltages along a capillary membrane.Thanks to the emerging Joule effect,the membrane-surface temperature and the associated O_(2) permeation flux could be adjusted.Here,the OTM is electrically and locally heated and reaches 900℃on the surface,whereas the surrounding of the membrane was maintained at 650℃.The O_(2)permeation flux reached for the electrified membranes was~3.7 NmL min^(-1)cm^(-2),corresponding to the flux obtained with an OTM non-electrified at 900℃.The influence of depositing a porous Ce_(0.8)Tb_(0.2)O_(2-δ) catalytic/protective layer on the outer membrane surface revealed that lower surface temperatures(830℃)were detected at the same imposed electric power.Finally,the electrification concept was demonstrated in a catalytic membrane reactor(CMR)where the oxidative dehydrogenation of ethane(ODHE)was carried out.ODHE reaction is very sensitive to temperature,and here,we demonstrate an improvement of the ethylene yield by reaching moderate temperatures in the reaction chamber while the O_(2) injection into the reaction can be easily fine-tuned.

关键词： Oxygen permeation Oxidative dehydrogenation of ethane Oxygen transport membranes Joule effect Mixed ionic-electronic conductors Catalytic membrane reactors

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Environmental drivers of long-term variations in the abundance of the red hocicudo mouse (Oxymycterus rufus) in Pampas agroecosystems

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Integrative Zoology 2024年第1期19卷 37-51页

作者： laura Mariel CALFAYAN Regino CAVIA Jimena FRAsCHINA Juan santiago GUIDOBONO Irene laura GOROsITO María BUsCH Laboratorio de Ecología de Poblaciones Departamento de EcologíaGenética y EvoluciónFacultad de Ciencias Exactas y NaturalesUniversidad de Buenos Aires and Instituto de EcologíaGenética y Evolución de Buenos Aires(IEGEBA)Buenos AiresArgentina

During the 20th century,there has been an ongoing agricultural expansion and global warming,two of the main determinants influencing biodiversity changes in Argentina.The red hocicudo mouse(Oxymycterus rufus)inhabits subtropical grasslands and riparian habitats and has increased its abundance in recent years in central Argentina agroecosystems.This paper describes the long-term temporal changes in O.rufus abundance in Exaltación de la Cruz department,Buenos Aires province,Argentina,in relation to weatherfluctuations and landscape features,as well as analyzes the spatio-temporal structure of captures of animals.We used generalized liner models,semi-variograms,the Mantel test,and autocorrelation functions for the analysis of rodent data obtained from trappings conducted between 1984 and 2014.O.rufus showed an increase in abundance across the years of study,with its distribution depending on landscape features,such as habitat types and the distance tofloodplains.Capture rates showed a spatio-temporal aggregation,suggesting expansion from previously occupied sites.O.rufus was more abundant at lower minimum temperatures in summer,higher precipitation in spring and summer,and lower precip-itations in winter.Weather conditions affected O.rufus abundance,but there was local variation that differed from global patterns of climate change.

关键词： agroecosystems climate change linear habitats Oxymycterus rufus rodent

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Circadian rhythm disruption and retinal dysfunction:a bidirectional link in Alzheimer’s disease?

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Neural Regeneration Research 2024年第9期19卷 1967-1972页

作者： laura Carrero DesireéAntequera Cristina Municio Eva Carro Group of Neurodegenerative Diseases Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpainNetwork Center for Biomedical Research in Neurodegenerative Diseases(CIBERNED)ISCIIIMadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpainNetwork Centre for Biomedical Research in Neurodegenerative Diseases(CIBERNED)ISCIIIMadridSpain

Dysfunction in circadian rhythms is a common occurrence in patients with Alzheimer’s disease.A predominant function of the retina is circadian synchronization,carrying information to the brain through the retinohypothalamic tract,which projects to the suprachiasmatic nucleus.Notably,Alzheimer’s disease hallmarks,including amyloid-β,are present in the retinas of Alzheimer’s disease patients,followed/associated by structural and functional disturbances.However,the mechanistic link between circadian dysfunction and the pathological changes affecting the retina in Alzheimer’s disease is not fully understood,although some studies point to the possibility that retinal dysfunction could be considered an early pathological process that directly modulates the circadian rhythm.

关键词： Alzheimer’s disease amyloid circadian rhythm neurodegeneration retina

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Probing the endoplasmic reticulummitochondria interaction in Alzheimer's disease:searching far and wide

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Neural Regeneration Research 2024年第10期19卷 2103-2104页

作者： Giulia Dematteis laura Tapella Dmitry Lim Department of Pharmaceutical sciences Universitàdel Piemonte Orientale“Amedeo Avogadro”NovaraItaly

Alzheimer's disease(AD)is the most frequent,form of dementia in elderly people and is an incurable disease with an exponentially growing number of cases.Extracellular deposition of amyloid-β(Aβ)plaques and intraneur... 详细信息

关键词： Alzheimer Aβ reticulum

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