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Antigen/adjuvant‐free liposome induces adjuvant effects for enhancing cancer immunotherapy 不含抗原/佐剂的脂质体诱导增强癌症免疫疗法的佐剂效应
Exploration Pub Date : 2024-07-17 DOI: 10.1002/exp.20230115
Qianqian Guo, Xiaoxuan Xu, Xiaojiang Lai, Jialin Duan, Dan Yan, Dangge Wang
{"title":"Antigen/adjuvant‐free liposome induces adjuvant effects for enhancing cancer immunotherapy","authors":"Qianqian Guo, Xiaoxuan Xu, Xiaojiang Lai, Jialin Duan, Dan Yan, Dangge Wang","doi":"10.1002/exp.20230115","DOIUrl":"https://doi.org/10.1002/exp.20230115","url":null,"abstract":"Cancer vaccines are promising to treat malignancy by delivering antigens and adjuvants to elicit host immunity. Beyond aluminum adjuvants, liposomes show efficient adjuvant effects through regulating the accumulation, internalization and release of payloads. However, it remains unknown that whether the liposome will perform intrinsic adjuvant effects in the absence of antigens and adjuvants. Herein, a library of antigen/adjuvant‐free liposomes with variable surface charges has been developed and it has been found that highly anionic liposomes show promising adjuvant effects for boosting immune responses. The anionic liposome mobilizes the MyD88 pathways of dendritic cells (DCs) to activate T helper cells and CD8+ T cells. The anionic liposomes enhance host immunity by regulating the population of Th1, Th2 and regulatory T cells (Tregs), and boost adaptive CD8+ T cells in lymphoid organs with good biosafety. It shows the most efficient protection against MC38 colorectal cancer in mice after a parallel injection of antigens and anionic liposomes. Overall, this study reveals that the surface charge of liposome affects its adjuvant efficiency and provides an anionic nanosized adjuvant formulation for enhancing immunization.","PeriodicalId":503118,"journal":{"name":"Exploration","volume":" 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141828504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Drug delivery pathways to the central nervous system via the brain glymphatic system circumventing the blood‐brain barrier 通过脑甘油系统绕过血脑屏障进入中枢神经系统的给药途径
Exploration Pub Date : 2024-07-09 DOI: 10.1002/exp.20240036
Xiang Wang, Yue Yin, Huaijuan Zhou, Bowen Chi, Ling Guan, Pei Li, Jinhua Li, Yilong Wang
{"title":"Drug delivery pathways to the central nervous system via the brain glymphatic system circumventing the blood‐brain barrier","authors":"Xiang Wang, Yue Yin, Huaijuan Zhou, Bowen Chi, Ling Guan, Pei Li, Jinhua Li, Yilong Wang","doi":"10.1002/exp.20240036","DOIUrl":"https://doi.org/10.1002/exp.20240036","url":null,"abstract":"The blood‐brain barrier (BBB) poses daunting challenges in treating diseases associated with the central nervous system (CNS). Recently, the traditional notion of the absence of the lymphatic system in the brain is evolving. The discovery of the glymphatic system in the brain has stimulated tremendous interest in developing new strategies for the treatment of CNS diseases. Leveraging the glymphatic system for CNS drug delivery may pave a new avenue to circumvent the BBB and achieve efficient drug delivery. The review focuses on the glymphatic system of the brain, discussing potential factors affecting its functions and exploring their connections with the meningeal lymphatic system. Finally, the review provides an overview of the drug delivery methods through the glymphatic system to circumvent BBB and regulate brain immunity. These innovative drug delivery methods may significantly improve drug utilization and create new avenues for the treatment of brain diseases.","PeriodicalId":503118,"journal":{"name":"Exploration","volume":"118 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141665326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Well‐defined nanostructures of high entropy alloys for electrocatalysis 用于电催化的定义明确的高熵合金纳米结构
Exploration Pub Date : 2024-07-02 DOI: 10.1002/exp.20230036
Jie Chen, Liping Ren, Xin Chen, Qi Wang, Chunying Chen, Jinpeng Fan, Shuai Wang, Vasileios Binas, Shaohua Shen
{"title":"Well‐defined nanostructures of high entropy alloys for electrocatalysis","authors":"Jie Chen, Liping Ren, Xin Chen, Qi Wang, Chunying Chen, Jinpeng Fan, Shuai Wang, Vasileios Binas, Shaohua Shen","doi":"10.1002/exp.20230036","DOIUrl":"https://doi.org/10.1002/exp.20230036","url":null,"abstract":"High‐entropy alloys (HEAs) have attracted significant attention for electrocatalytic energy conversion by virtue of their promisingly high efficiency, stability, and low cost. Recently, encouraging progress has been made in tuning the structure and composition of HEAs used in electrolyzers and fuel cells. However, the understanding on the synthetic methods and the structure‐property‐performance relationship of well‐defined HEAs nanostructures is still inadequate. To gain insight into the future research directions on HEAs for electrocatalysis, in this paper, the synthetic methods commonly used to obtain well‐defined HEAs nanostructures (0D nanoparticles, 1D nanowires, 2D nanosheets/nanoplates, 3D nanoporous structures, and other three‐dimensional morphologies) are first summarized. Then, the authors discuss the application of well‐defined HEAs nanostructures in several typical electrocatalytic reactions, including hydrogen evolution reaction, oxygen evolution reaction, oxygen reduction reaction, alcohol oxidation reaction, carbon dioxide reduction reaction, nitrogen reduction reaction, and formic acid oxidation reaction. Finally, a practical perspective on the future research directions on well‐defined HEAs nanostructured electrocatalysts is provided.","PeriodicalId":503118,"journal":{"name":"Exploration","volume":"6 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141683958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endoperoxide‐enhanced self‐assembled ROS producer as intracellular prodrugs for tumor chemotherapy and chemodynamic therapy 内过氧化物增强型自组装 ROS 生成器作为细胞内原药用于肿瘤化疗和化学动力疗法
Exploration Pub Date : 2024-02-09 DOI: 10.1002/exp.20230127
Junjie Tang, Yadong Liu, Yifan Xue, Zhaozhong Jiang, Baizhu Chen, Jie Liu
{"title":"Endoperoxide‐enhanced self‐assembled ROS producer as intracellular prodrugs for tumor chemotherapy and chemodynamic therapy","authors":"Junjie Tang, Yadong Liu, Yifan Xue, Zhaozhong Jiang, Baizhu Chen, Jie Liu","doi":"10.1002/exp.20230127","DOIUrl":"https://doi.org/10.1002/exp.20230127","url":null,"abstract":"Prodrug‐based self‐assembled nanoparticles (PSNs) with tailored responses to tumor microenvironments show a significant promise for chemodynamic therapy (CDT) by generating highly toxic reactive oxygen species (ROS). However, the insufficient level of intracellular ROS and the limited drug accumulation remain major challenges for further clinical transformation. In this study, the PSNs for the delivery of artesunate (ARS) are demonstrated by designing the pH‐responsive ARS‐4‐hydroxybenzoyl hydrazide (HBZ)‐5‐amino levulinic acid (ALA) nanoparticles (AHA NPs) with self‐supplied ROS for excellent chemotherapy and CDT. The PSNs greatly improved the loading capacity of artesunate and the ROS generation from endoperoxide bridge using the electron withdrawing group attached directly to C10 site of artesunate. The ALA and ARS‐HBZ could be released from AHA NPs under the cleavage of hydrazone bonds triggered by the acidic surroundings. Besides, the ALA increased the intracellular level of heme in mitochondria, further promoting the ROS generation and lipid peroxidation with ARS‐HBZ for excellent anti‐tumor effects. Our study improved the chemotherapy of ARS through the chemical modification, pointing out the potential applications in the clinical fields.","PeriodicalId":503118,"journal":{"name":"Exploration","volume":" 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139788632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cornea‐SELEX for aptamers targeting the surface of eyes and liposomal drug delivery 针对眼睛表面和脂质体给药的适配体的 Cornea-SELEX
Exploration Pub Date : 2024-02-09 DOI: 10.1002/exp.20230008
Ka-Ying Wong, Yibo Liu, Man-Sau Wong, Juewen Liu
{"title":"Cornea‐SELEX for aptamers targeting the surface of eyes and liposomal drug delivery","authors":"Ka-Ying Wong, Yibo Liu, Man-Sau Wong, Juewen Liu","doi":"10.1002/exp.20230008","DOIUrl":"https://doi.org/10.1002/exp.20230008","url":null,"abstract":"Cornea is the major barrier to drug delivery to the eye, which results in low bioavailability and poor efficacy of topical eye treatment. In this work, we first select cornea‐binding aptamers using tissue‐SELEX on pig cornea. The top two abundant aptamers, Cornea‐S1 and Cornea‐S2, could bind to pig cornea, and their Kd values to human corneal epithelial cells (HCECs) were 361 and 174 nм, respectively. Aptamer‐functionalized liposomes loaded with cyclosporine A (CsA) were developed as a treatment for dry eye diseases. The Kd of Cornea‐S1‐ or Cornea‐S2‐functionalized liposomes reduces to 1.2 and 15.1 nм, respectively, due to polyvalent binding. In HCECs, Cornea‐S1 or Cornea‐S2 enhanced liposome uptake within 15 min and extended retention to 24 h. Aptamer CsA liposomes achieved similar anti‐inflammatory and tight junction modulation effects with ten times less CsA than a free drug. In a rabbit dry eye disease model, Cornea‐S1 CsA liposomes demonstrated equivalence in sustaining corneal integrity and tear break‐up time when compared to commercial CsA eye drops while utilizing a lower dosage of CsA. The aptamers obtained from cornea‐SELEX can serve as a general ligand for ocular drug delivery, suggesting a promising avenue for the treatment of various eye diseases and even other diseases.","PeriodicalId":503118,"journal":{"name":"Exploration","volume":" 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139789930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling the importance of the interface in nanocomposite cathodes for proton‐conducting solid oxide fuel cells 揭示质子传导型固体氧化物燃料电池纳米复合阴极界面的重要性
Exploration Pub Date : 2024-02-01 DOI: 10.1002/exp.20230082
Yanru Yin, Yifan Wang, Nan Yang, Lei Bi
{"title":"Unveiling the importance of the interface in nanocomposite cathodes for proton‐conducting solid oxide fuel cells","authors":"Yanru Yin, Yifan Wang, Nan Yang, Lei Bi","doi":"10.1002/exp.20230082","DOIUrl":"https://doi.org/10.1002/exp.20230082","url":null,"abstract":"Designing a high‐performance cathode is essential for the development of proton‐conducting solid oxide fuel cells (H‐SOFCs), and nanocomposite cathodes have proven to be an effective means of achieving this. However, the mechanism behind the nanocomposite cathodes' remarkable performance remains unknown. Doping the Co element into BaZrO3 can result in the development of BaCoO3 and BaZr0.7Co0.3O3 nanocomposites when the doping concentration exceeds 30%, according to the present study. The construction of the BaCoO3/BaZr0.7Co0.3O3 interface is essential for the enhancement of the cathode catalytic activity, as demonstrated by thin‐film studies using pulsed laser deposition to simulate the interface of the BCO and BZCO individual particles and first‐principles calculations to predict the oxygen reduction reaction steps. Eventually, the H‐SOFC with a BaZr0.4Co0.6O3 cathode produces a record‐breaking power density of 2253 mW cm−2 at 700°C.","PeriodicalId":503118,"journal":{"name":"Exploration","volume":"7 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139886935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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