Small Science最新文献_第9页

Microfluidic Production of Spatially Structured Biomimetic Microgels as Compartmentalized Artificial Cells. 空间结构仿生微凝胶作为区隔人工细胞的微流控制备。

IF 11.1

Small Science Pub Date : 2025-02-06 eCollection Date: 2025-04-01 DOI: 10.1002/smsc.202400320

Matthew E Allen, James W Hindley, Robert V Law, Oscar Ces, Yuval Elani

{"title":"Microfluidic Production of Spatially Structured Biomimetic Microgels as Compartmentalized Artificial Cells.","authors":"Matthew E Allen, James W Hindley, Robert V Law, Oscar Ces, Yuval Elani","doi":"10.1002/smsc.202400320","DOIUrl":"10.1002/smsc.202400320","url":null,"abstract":"Artificial cells serve as promising micro-robotic platforms that replicate cellular features. One ubiquitous characteristic of living cells is compartmentalization of content in distinct and well-defined locations. Herein, a microfluidic strategy to mimic compartmentalization is developed through the production of micron-scale two and three compartment biomimetic microgels, where hydrogel compartment number, composition, size, and shape can be controlled. Our lab-on-chip system enables the incorporation of various synthetic organelles into spatially separated compartments within the microgels. This design concept allows for the introduction of a variety of individually triggered bioinspired behaviors, including protein capture, enzyme-mediated content release, and stimuli-triggered motility, each isolated in a distinct compartment enabling the use of the microgels as compartmentalized artificial cells. With this approach, the division of content and function seen in biological cells can be mirrored, which will underpin the generation of increasingly sophisticated and functional soft matter microdevices using bottom-up synthetic biology principles.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":"5 4","pages":"2400320"},"PeriodicalIF":11.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12245075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Programming-Assisted Imaging of Cellular Nitric Oxide Efflux Gradients and Directionality via Carbon Nanotube Sensors. 基于碳纳米管传感器的细胞一氧化氮外排梯度和方向性的编程辅助成像。

IF 11.1

Small Science Pub Date : 2025-02-04 eCollection Date: 2025-04-01 DOI: 10.1002/smsc.202400493

Ivon Acosta Ramirez, Sruti Das Choudhury, Carley Conover, Omer Sadak, Nicole M Iverson

{"title":"Programming-Assisted Imaging of Cellular Nitric Oxide Efflux Gradients and Directionality via Carbon Nanotube Sensors.","authors":"Ivon Acosta Ramirez, Sruti Das Choudhury, Carley Conover, Omer Sadak, Nicole M Iverson","doi":"10.1002/smsc.202400493","DOIUrl":"10.1002/smsc.202400493","url":null,"abstract":"Cell communication via chemical signaling depends on spatial and temporal concentration changes. Nitric oxide (NO), a gaseous signaling molecule, is critical in physiological and pathological processes. However, current NO sensing methods lack the spatiotemporal resolution necessary to study subcellular NO efflux. This study introduces an innovative sensory platform utilizing single-walled carbon nanotubes (SWNT) as an optical transducer for the spatial and temporal detection of extracellular NO. The platform quantifies NO diffusion gradients produced by human (THP-1) and murine (RAW 264.7) macrophage cells. The uniform fluorescence distribution of the nanoarray enables precise analysis of NO efflux directionality, both under and surrounding the cell. It is demonstrated that cellular adhesion to the surface of the sensory platform does not affect its fluorescence functionality or sensing response rate. By combining the platform's high spatiotemporal resolution with the advanced analysis methods, the SWNT sensor platform offers a robust tool for studying extracellular NO dynamics within the cellular microenvironment. This work lays the foundation for advanced diagnostic and therapeutic tools elucidating NO cellular communication analysis.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":"5 4","pages":"2400493"},"PeriodicalIF":11.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12245041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vortex Fluidic Mediated Synthesis of Enhanced Hydrogen Producing Magnetic Gold. 涡旋流控合成强化产氢磁性金。

IF 11.1

Small Science Pub Date : 2025-02-03 eCollection Date: 2025-04-01 DOI: 10.1002/smsc.202400449

Badriah M Alotaibi, Soraya Rapheima, Po-Wei Yu, Xianjue Chen, Tanglaw Roman, Christopher T Gibson, Tiexin Lib, Dechao Chen, Elsa Antunes, Qin Li, Mats R Anderson, Nadim Darwish, Colin L Raston

{"title":"Vortex Fluidic Mediated Synthesis of Enhanced Hydrogen Producing Magnetic Gold.","authors":"Badriah M Alotaibi, Soraya Rapheima, Po-Wei Yu, Xianjue Chen, Tanglaw Roman, Christopher T Gibson, Tiexin Lib, Dechao Chen, Elsa Antunes, Qin Li, Mats R Anderson, Nadim Darwish, Colin L Raston","doi":"10.1002/smsc.202400449","DOIUrl":"10.1002/smsc.202400449","url":null,"abstract":"While bulk gold is well known to be diamagnetic, there is growing experimental and theoretical work supporting the formation of nano gold with unconventional magnetic properties. However, access to such magnetic gold nanoparticles at scale is limited. It is established that magnetic gold particles are readily accessible when exposing aqueous solutions of auric acid (H[AuCl4]) to UV irradiation (λ = 254 nm) under high shear in a vortex fluidic device (VFD), as a photo-contact electrification process. Thin films of liquid in the VFD down to ≈200 μm thick are generated in a tilted rapidly rotating angled glass tube with induced mechanical energy imparted under high shear, which when exposed to UV, reduces Au3+ to elemental gold without the need for adding reducing agents, unlike in the conventional synthesis of nano gold particles. The use of magnetic force microscopy (MFM) is reported to show that VFD-generated 2D gold sheets have magnetic gold nanoparticles embedded in them, with the material electron paramagnetic resonance active. A report is made on theoretical insights into the origin of the magnetism and that the material shows a dramatic enhancement of catalytic activity in the hydrogen generation reaction relative to using traditionally produced gold nanoparticles of comparable size.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":"5 4","pages":"2400449"},"PeriodicalIF":11.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toward Personalized Immunotherapeutic Drug Monitoring with Multiplexed Extended-Gate Field-Effect-Transistor Biosensors. 利用多路扩展门场效应晶体管生物传感器实现个性化免疫治疗药物监测。

IF 11.1

Small Science Pub Date : 2025-02-03 eCollection Date: 2025-05-01 DOI: 10.1002/smsc.202400515

Trang-Anh Nguyen-Le, Christin Neuber, Isli Cela, Željko Janićijević, Liliana Rodrigues Loureiro, Lydia Hoffmann, Anja Feldmann, Michael Bachmann, Larysa Baraban

{"title":"Toward Personalized Immunotherapeutic Drug Monitoring with Multiplexed Extended-Gate Field-Effect-Transistor Biosensors.","authors":"Trang-Anh Nguyen-Le, Christin Neuber, Isli Cela, Željko Janićijević, Liliana Rodrigues Loureiro, Lydia Hoffmann, Anja Feldmann, Michael Bachmann, Larysa Baraban","doi":"10.1002/smsc.202400515","DOIUrl":"10.1002/smsc.202400515","url":null,"abstract":"The selection and optimization of therapies for cancer patients urgently need personalization. Portable point-of-care electronic biosensors emerge as a groundbreaking solution contributing to better decision-making in precision oncology. In this study, the innovative use of extended-gate field-effect-transistor (EG-FET) biosensors is showcased for monitoring the concentration and pharmacokinetics of immunotherapeutic drugs in vivo. Complementary positron emission tomography and radioactivity biodistribution studies in mice validate the EG-FET measurements. Herein, a novel indirect assay format is also introduced for detecting target modules (TMs) in an adapter chimeric antigen receptor T-cell therapy model, effectively addressing the current limitations of potentiometric measurements. In pharmacokinetic evaluations, the EG-FET biosensor performance aligns with standard radioactivity measurements, revealing the distinct lifespans of small-sized single-chain-fragment-variable-derived TMs (15 min) and larger IgG4-derived TMs (14 h). Advantageously, the EG-FET sensors exhibit exceptional sensitivity and fulfill the requirements for immunotherapeutic drug monitoring without complex radioactive labeling, which is indispensable. In these promising findings, the exploration of next-generation electronic biosensors as therapeutic monitoring tools is advocated for. With their cost, size, and response time advantages, these biosensors hold immense potential for advancing personalized oncology, transcending the conventional diagnostic roles typically highlighted in the literature.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":"5 5","pages":"2400515"},"PeriodicalIF":11.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biodegradable Piezoelectric Micro- and Nanomaterials for Regenerative Medicine, Targeted Therapy, and Microrobotics. 用于再生医学、靶向治疗和微型机器人的可生物降解压电微纳米材料。

IF 11.1

Small Science Pub Date : 2025-01-28 eCollection Date: 2025-04-01 DOI: 10.1002/smsc.202400439

Lorenzo Vannozzi, Carlotta Pucci, Diego Trucco, Claudia Turini, Semih Sevim, Salvador Pané, Leonardo Ricotti

{"title":"Biodegradable Piezoelectric Micro- and Nanomaterials for Regenerative Medicine, Targeted Therapy, and Microrobotics.","authors":"Lorenzo Vannozzi, Carlotta Pucci, Diego Trucco, Claudia Turini, Semih Sevim, Salvador Pané, Leonardo Ricotti","doi":"10.1002/smsc.202400439","DOIUrl":"10.1002/smsc.202400439","url":null,"abstract":"Piezoelectric micro- and nanomaterials can generate local electrical signals when subjected to mechanical stress, a phenomenon that can be exploited to trigger beneficial effects at the cell and tissue level. In recent years, research on biodegradable piezoelectric material has gained momentum, as these materials can degrade after fulfilling their function. Thus, they promise to considerably impact regenerative medicine, targeted therapy, and microrobotics, with better chances to match regulatory requirements with respect to their nondegradable counterparts. This review offers a comprehensive overview of recent advancements in biodegradable piezoelectric micro- and nanomaterials, focusing on their piezoelectric mechanisms, material types, and methods to enhance their properties. Current characterization techniques, emphasizing both piezoelectricity and biodegradability at the micro/nano scale, are also discussed. Furthermore, it is discussed how to use these materials in intelligent platforms for regenerative medicine and responsive drug delivery systems. The application of piezoelectric micro- and nanomaterials in microrobotics is also examined, particularly their potential for minimally invasive procedures. Finally, challenges and future directions are highlighted, underscoring the importance of biodegradable piezoelectric materials as versatile platforms for advancing biomedical technologies.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":"5 4","pages":"2400439"},"PeriodicalIF":11.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12245126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhanced Control of Single Crystalline Ag Dendritic Growth on Al Foil via Galvanic Displacement and Simultaneous Oxidation of D-Glucose. 电驱和同时氧化d -葡萄糖增强对Al箔上银枝晶生长的控制

IF 11.1

Small Science Pub Date : 2025-01-28 eCollection Date: 2025-04-01 DOI: 10.1002/smsc.202400478

Lidija D Rafailović, Stefan M Noisternig, Jana Bischoff, Christian Rentenberger, Daniel Bautista-Anguis, Huaping Sheng, Christoph Gammer, Jia Min Chin, Adam Elbataioui, Huanqing Zhang, Jürgen Eckert, Tomislav Lj Trišović

{"title":"Enhanced Control of Single Crystalline Ag Dendritic Growth on Al Foil via Galvanic Displacement and Simultaneous Oxidation of D-Glucose.","authors":"Lidija D Rafailović, Stefan M Noisternig, Jana Bischoff, Christian Rentenberger, Daniel Bautista-Anguis, Huaping Sheng, Christoph Gammer, Jia Min Chin, Adam Elbataioui, Huanqing Zhang, Jürgen Eckert, Tomislav Lj Trišović","doi":"10.1002/smsc.202400478","DOIUrl":"10.1002/smsc.202400478","url":null,"abstract":"A facile synthesis platform for the formation of stable single crystalline Ag dendrites is demonstrated. Using a porous electrospun polyacrylonitrile nanofiber network on Al foil as a template facilitates more uniform dendritic growth in the presence of D-glucose. In contrast, a denser polymer network restricts the nucleation site availability on the Al foil, highlighting the critical role of the substrate. The growth formation of silver dendrites is reduced in the solution when two simultaneous processes occur: The electroreduction of Ag+ in the D-glucose solution and galvanic displacement driven by the interaction of Ag+ with the aluminum substrate. High-resolution transmission electron microscopy analysis shows the single crystalline nature of Ag dendrites grown from the Al substrate, revealing atomic structures with closely packed layers forming highly faulted face-centered cubic and hexagonal close-packed structures. The remarkable long-term stability of Ag dendrites is primarily attributed to their single crystalline structure, with additional contributions from capping by D-gluconic acid, as confirmed by Raman analysis. This novel approach to the generation of highly stable Ag dendrites has significant potential for applications such as surface-enhanced Raman scattering, which has to date been considered to be very sensitive to environmental effects.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":"5 4","pages":"2400478"},"PeriodicalIF":11.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12245025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Modular Bacteriophage T4 Nanoparticle Platform Enables Rapid Design of Dual COVID-19-Flu Mucosal Vaccines. 模块化T4噬菌体纳米颗粒平台可快速设计新型covid -19流感黏膜双疫苗

IF 11.1

Small Science Pub Date : 2025-01-28 eCollection Date: 2025-04-01 DOI: 10.1002/smsc.202400580

Jingen Zhu, Jian Sha, Himanshu Batra, Swati Jain, Xiaorong Wu, Emily K Hendrix, Paul B Kilgore, Keer Sun, Kenneth S Plante, Jessica A Plante, Jordyn Walker, Pan Tao, Ashok K Chopra, Venigalla B Rao

{"title":"A Modular Bacteriophage T4 Nanoparticle Platform Enables Rapid Design of Dual COVID-19-Flu Mucosal Vaccines.","authors":"Jingen Zhu, Jian Sha, Himanshu Batra, Swati Jain, Xiaorong Wu, Emily K Hendrix, Paul B Kilgore, Keer Sun, Kenneth S Plante, Jessica A Plante, Jordyn Walker, Pan Tao, Ashok K Chopra, Venigalla B Rao","doi":"10.1002/smsc.202400580","DOIUrl":"10.1002/smsc.202400580","url":null,"abstract":"A multivalent, rapidly deployable, mucosal vaccine platform is desperately needed to prevent acquisition and transmission of respiratory infections during epidemics and pandemics. No such approved platform currently exists and virtually all under investigation use infectious viruses that have safety concerns and are not amenable for multivalent engineering. Herein, a non-infectious biomaterial platform is presented, the bacteriophage T4 nanoparticle endowed with unique features for modular engineering, which is exploited to design dual COVID-Flu mucosal vaccines. By leveraging T4's natural affinity to nasal mucosa, in vivo CRISPR engineering, and in vitro SpyCatcher-SpyTag conjugation, hundreds of antigen molecules are incorporated from SARS-CoV-2 and influenza viruses into one nanoparticle. These include spike and hemagglutinin trimers and M2e peptides decorating the capsid while encapsulating matrix or nucleocapsid proteins inside, thereby achieving unprecedented antigen density and diversity, a pinnacle nanoparticle design. Intranasal administration of this adjuvant-free T4-CoV-Flu vaccine induces remarkable mucosal immunity against both respiratory pathogens, including high-titer neutralizing antibodies and secretory IgA, lung-resident CD4+/CD8+ T cells, diverse memory B cells, and complete protection against SARS-CoV-2 and influenza challenges. Coupled with its scalability in bacterial systems, thermostability, and adjuvant- and needle-free delivery, T4 presents an extraordinary platform to design potent mucosal vaccines against pandemic threats.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":"5 4","pages":"2400580"},"PeriodicalIF":11.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12245071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ENT-1-Targeted Polymersomes to Enhance the Efficacy of Methotrexate in Choriocarcinoma Treatment. ent -1靶向聚合体增强甲氨蝶呤治疗绒毛膜癌的疗效。

IF 11.1

Small Science Pub Date : 2025-01-28 eCollection Date: 2025-07-01 DOI: 10.1002/smsc.202400361

Babak Mamnoon, Ana Paula Mesquita Souza, Tetiana Korzun, Maureen K Baldwin, K Shitaljit Sharma, Oleh Taratula, Yoon Tae Goo, Prem Singh, Vladislav Grigoriev, Aryan Lakhanpal, Olena R Taratula

{"title":"ENT-1-Targeted Polymersomes to Enhance the Efficacy of Methotrexate in Choriocarcinoma Treatment.","authors":"Babak Mamnoon, Ana Paula Mesquita Souza, Tetiana Korzun, Maureen K Baldwin, K Shitaljit Sharma, Oleh Taratula, Yoon Tae Goo, Prem Singh, Vladislav Grigoriev, Aryan Lakhanpal, Olena R Taratula","doi":"10.1002/smsc.202400361","DOIUrl":"10.1002/smsc.202400361","url":null,"abstract":"Gestational choriocarcinoma (CC) is a rare and highly malignant cancer originating from the trophoblastic layers of the placenta. Currently, methotrexate (MTX) is the first-line treatment for CC; however, due to the aggressive and metastatic nature of CC, multiple doses are often required, leading to severe side effects from the lack of tumor specificity. The first targeted MTX-loaded polymersomes (Ps) designed for efficient drug delivery to CC tumors are introduced. The modification of these Ps nanoplatforms with guanosine (Gn), which targets the ENT-1 transporter overexpressed in CC cells, significantly enhances tumor uptake. Upon internalization by CC cells, the disulfide bonds in the Ps are reduced by high intracellular glutathione levels, causing Ps disintegration and efficient drug release. Biodistribution studies also reveal significant accumulation in subcutaneous CC tumors with minimal distribution in major organs. The ENT-1-targetedpolymersomes show twice the tumor accumulation compared to the nontargeted ones based on in-vivo fluorescence imaging. ENT-1-targeted MTX-loaded polymersomes (Gn-MTX@SS-Ps) achieve significantly greater tumor shrinkage in mice, reducing tumors by 30% more than nontargeted MTX@SS-Ps and 75% more than free MTX at the same dosage regimen. Consequently, developed CC-targeted MTX-loaded polymer-based delivery system holds the potential to significantly enhance the treatment of CC.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":"5 7","pages":"2400361"},"PeriodicalIF":11.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Yeast Complementation Assays Demonstrating the Importance of the Affinity Tag Position in Membrane Protein Purification, as Exemplified by HpUreI, the pH-Gated Urea Channel of Helicobacter pylori. 酵母互补实验证明了亲和标签位置在膜蛋白纯化中的重要性，如幽门螺杆菌ph门控尿素通道HpUreI。

IF 11.1

Small Science Pub Date : 2025-01-27 eCollection Date: 2025-05-01 DOI: 10.1002/smsc.202400571

Anna Stoib, Sahar Shojaei, Christine Siligan, Andreas Horner

{"title":"Yeast Complementation Assays Demonstrating the Importance of the Affinity Tag Position in Membrane Protein Purification, as Exemplified by HpUreI, the pH-Gated Urea Channel of Helicobacter pylori.","authors":"Anna Stoib, Sahar Shojaei, Christine Siligan, Andreas Horner","doi":"10.1002/smsc.202400571","DOIUrl":"10.1002/smsc.202400571","url":null,"abstract":"Affinity tags are a crucial component in protein purification. Despite several indications that they can influence protein structure and function, this influence is often unknown or disregarded. This unnecessarily introduces ambiguity in the interpretation of in vitro data. To illustrate that, urea and ammonia yeast complementation assays are used as a screening tool to assess functional differences in various affinity tag positions, compared to the WT protein, using HpUreI, an acid-gated urea channel of Helicobacter pylori. Yeast complementation assays test the pH-dependent functionality of exogenous proteins expressed in deletion strains by observing growth. If the exogenous protein is able to replace the function of the deleted endogenous protein, yeast cells can demonstrate growth under specific assay conditions. The overall tag position and even a minor amount of residual N- or C-terminal amino acids following tag cleavage exert a solute-specific influence on HpUreI functionality, suggesting a complex solute selectivity mechanism and underscores the necessity for in vivo characterization. This cost-effective yeast complementation assay can be adapted to test a broad range of solutes. It can be used as a preliminary screening tool for affinity tag positions or protein mutations before quantitative in vitro protein characterization.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":"5 5","pages":"2400571"},"PeriodicalIF":11.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intravitreal Administration of Adalimumab-Loaded Poly(Lactic-co-Glycolic Acid) Nanoparticles: Effects on Biodistribution and Pharmacokinetics. 载阿达木单抗聚乳酸-羟基乙酸纳米颗粒的玻璃体内给药：对生物分布和药代动力学的影响。

IF 11.1

Small Science Pub Date : 2025-01-27 eCollection Date: 2025-04-01 DOI: 10.1002/smsc.202400494

Xurxo García-Otero, Rubén Varela-Fernández, Andrea Cuartero-Martínez, Noemí Gómez-Lado, Miguel González-Barcia, Cristina Mondelo-García, Carolina Feitosa, Pablo Aguiar, Anxo Fernández-Ferreiro, Francisco J Otero-Espinar

{"title":"Intravitreal Administration of Adalimumab-Loaded Poly(Lactic-co-Glycolic Acid) Nanoparticles: Effects on Biodistribution and Pharmacokinetics.","authors":"Xurxo García-Otero, Rubén Varela-Fernández, Andrea Cuartero-Martínez, Noemí Gómez-Lado, Miguel González-Barcia, Cristina Mondelo-García, Carolina Feitosa, Pablo Aguiar, Anxo Fernández-Ferreiro, Francisco J Otero-Espinar","doi":"10.1002/smsc.202400494","DOIUrl":"10.1002/smsc.202400494","url":null,"abstract":"Adalimumab, a monoclonal antibody used for treating inflammatory diseases, including eye diseases, faces challenges in biodistribution and targeted delivery. Nanoparticle (NP)-based drug delivery systems have shown promise in enhancing the pharmacokinetic profiles of biologic drugs. This study aims to develop, and characterize intravitreal adalimumab-loaded poly(lactic-co-glycolic acid) (PLGA) NPs to improve antibody distribution and therapeutic efficacy. Characterization studies, morphological examination, and quantitative, stability, and physical properties are conducted. In vitro release kinetics are assessed using a dialysis membrane method. In vivo biodistribution is studied in rats after intravitreal administration by Positron Emission Tomography/Computed Tomography imaging. The optimized NPs were spherical (around 300 nm) with a surface charge of about -20 mV. Encapsulation efficiency and drug loading reach values close to 100%. Stability studies showed minimal changes in particle size and drug content. In vitro release showed a biphasic pattern with an initial burst release followed by sustained release. Safety studies indicated no significant cytotoxicity or adverse effects. The adalimumab-loaded PLGA NPs demonstrate favorable physicochemical characteristics, stability, and release profiles. In vivo distribution revealed a change in the antibody's distribution pattern after intravitreal administration via NPs encapsulation. These findings suggest the potential for enhanced therapeutic outcomes and warrant further investigation in disease-specific models to explore the clinical potential of this NP-based delivery system.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":"5 4","pages":"2400494"},"PeriodicalIF":11.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12245000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0