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1.
Inside Cover: MiniAp‐4: A Venom‐Inspired Peptidomimetic for Brain Delivery (Angew. Chem. Int. Ed. 2/2016) 下载免费PDF全文
Dr. Benjamí Oller‐Salvia Dr. Macarena Sánchez‐Navarro Sonia Ciudad Marc Guiu Pol Arranz‐Gibert Cristina Garcia Dr. Roger R. Gomis Prof. Roméo Cecchelli Dr. Jesús García Prof. Ernest Giralt Dr. Meritxell Teixidó 《Angewandte Chemie (International ed. in English)》2016,55(2):454-454
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Hyun Su Min Hyun Jin Kim Mitsuru Naito Satomi Ogura Kazuko Toh Kotaro Hayashi Beob Soo Kim Shigeto Fukushima Yasutaka Anraku Kanjiro Miyata Kazunori Kataoka 《Angewandte Chemie (International ed. in English)》2020,59(21):8173-8180
Current antisense oligonucleotide (ASO) therapies for the treatment of central nervous system (CNS) disorders are performed through invasive administration, thereby placing a major burden on patients. To alleviate this burden, we herein report systemic ASO delivery to the brain by crossing the blood–brain barrier using glycemic control as an external trigger. Glucose‐coated polymeric nanocarriers, which can be bound by glucose transporter‐1 expressed on the brain capillary endothelial cells, are designed for stable encapsulation of ASOs, with a particle size of about 45 nm and an adequate glucose‐ligand density. The optimized nanocarrier efficiently accumulates in the brain tissue 1 h after intravenous administration and exhibits significant knockdown of a target long non‐coding RNA in various brain regions, including the cerebral cortex and hippocampus. These results demonstrate that the glucose‐modified polymeric nanocarriers enable noninvasive ASO administration to the brain for the treatment of CNS disorders. 相似文献
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Maria Gregori Daniela Bertani Emanuela Cazzaniga Antonina Orlando Michele Mauri Alberto Bianchi Francesca Re Silvia Sesana Stefania Minniti Maura Francolini Alfredo Cagnotto Mario Salmona Luca Nardo Domenico Salerno Francesco Mantegazza Massimo Masserini Roberto Simonutti 《Macromolecular bioscience》2015,15(12):1687-1697
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Alzheimer's disease (AD) is an incurable neurodegenerative brain disorder that exhibits clear pathologic changes in the hippocampus. Traditional drug delivery systems are ineffective due to the existence of the blood–brain barrier (BBB). In this study, an efficient, stable, and easily constructed nanosystem (CB‐Gd‐Cy5.5) based on the cholera toxin B subunit (CB) is designed to improve the efficiency of drug delivery to the brain, especially the hippocampus. Through intranasal administration, CB‐Gd‐Cy5.5 is easily delivered to the brain without intervention by the BBB. The CB in CB‐Gd‐Cy5.5 is used for specifically combining with the monosialoganglioside GM1, which is widely found in the hippocampus. This nanosystem exhibits impressive performance in accumulating in the hippocampus. In addition, the good magnetic resonance imaging (MRI) capability of CB‐Gd‐Cy5.5 can satisfy the monitoring of AD in the different stages. 相似文献
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Applying the Retro‐Enantio Approach To Obtain a Peptide Capable of Overcoming the Blood–Brain Barrier 下载免费PDF全文
Dr. Roger Prades Benjamí Oller‐Salvia Dr. Susanne M. Schwarzmaier Dr. Javier Selva Dr. María Moros Matilde Balbi Dr. Valeria Grazú Dr. Jesus M. de La Fuente Prof. Gustavo Egea Prof. Nikolaus Plesnila Dr. Meritxell Teixidó Prof. Ernest Giralt 《Angewandte Chemie (International ed. in English)》2015,54(13):3967-3972
The blood–brain barrier (BBB) is a formidable physical and enzymatic barrier that tightly controls the passage of molecules from the blood to the brain. In fact, less than 2 % of all potential neurotherapeutics are able to cross it. Here, by applying the retro‐enantio approach to a peptide that targets the transferrin receptor, a full protease‐resistant peptide with the capacity to act as a BBB shuttle was obtained and thus enabled the transport of a variety of cargos into the central nervous system. 相似文献
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Xiaoli Wei Dr. Changyou Zhan Qing Shen Prof. Wei Fu Cao Xie Jie Gao Chunmei Peng Prof. Ping Zheng Prof. Weiyue Lu 《Angewandte Chemie (International ed. in English)》2015,54(10):3023-3027
Lysosomes of brain capillary endothelial cells are implicated in nicotine acetylcholine receptor (nAChR)‐mediated transcytosis and act as an enzymatic barrier for the transport of peptide ligands to the brain. A D ‐peptide ligand of nAChRs (termed DCDX), which binds to nAChRs with an IC50 value of 84.5 nM , was developed by retro–inverso isomerization. DCDX displayed exceptional stability in lysosomal homogenate and serum, and demonstrated significantly higher transcytosis efficiency in an in vitro blood–brain barrier monolayer compared with the parent L ‐peptide. When modified on liposomal surface, DCDX facilitated significant brain‐targeted delivery of liposomes. As a result, brain‐targeted delivery of DCDX modified liposomes enhanced therapeutic efficiency of encapsulated doxorubicin for glioblastoma. This study illustrates the importance of ligand stability in nAChRs‐mediated transcytosis, and paves the way for developing stable brain‐targeted entities. 相似文献
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Chaoqiang Qiao Ruili Zhang Yongdong Wang Qian Jia Xiaofei Wang Zuo Yang Tengfei Xue Renchuan Ji Xiufang Cui Zhongliang Wang 《Angewandte Chemie (International ed. in English)》2020,59(39):16982-16988
The blood–brain barrier (BBB) restricts access to the brain of more than 98 % of therapeutic agents and is largely responsible for treatment failure of glioblastoma multiforme (GBM). Therefore, it is of great importance to develop a safe and efficient strategy for more effective drug delivery across the BBB into the brain. Inspired by the extraordinary capability of rabies virus (RABV) to enter the central nervous system, we report the development and evaluation of the metal–organic framework‐based nanocarrier MILB@LR, which closely mimicked both the bullet‐shape structure and surface functions of natural RABV. MILB@LR benefited from a more comprehensive RABV‐mimic strategy than mimicking individual features of RABV and exhibited significantly enhanced BBB penetration and brain tumor targeting. MILB@LR also displayed superior inhibition of tumor growth when loaded with oxaliplatin. The results demonstrated that MILB@LR may be valuable for GBM targeting and treatment. 相似文献
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Mirjam Clemens‐Hemmelmann Christiane Kuffner Verena Metz Linda Kircher Ulrich Schmitt Christoph Hiemke Rolf Postina Rudolf Zentel 《Macromolecular bioscience》2016,16(5):655-665
Medical treatment of diseases of the central nervous system requires transport of drugs across the blood–brain barrier (BBB). Here, it is extended previously in vitro experiments with a model compound to show that the non‐water‐soluble and brain‐impermeable drug domperidone (DOM) itself can be enriched in the brain by use of an amphiphilic copolymer as a carrier. This carrier consists of poly(N‐(2‐hydroxypropyl)‐methacrylamide), statistically copolymerized with 10 mol% hydrophobic lauryl methacrylate, into whose micellar aggregates DOM is noncovalently absorbed. As tested in a BBB model efficient transport of DOM across, the BBB is achievable over a wide range of formulations, containing 0.8 to 35.5 wt% domperidone per copolymer. In neither case, the polymer itself is translocated across the BBB model. In vivo experiments in mice show that already 10 min after intraperitoneal injection of the polymer/domperidone (PolyDOM) formulation, domperidone can be detected in blood and in the brain. Highest serum and brain levels of domperidone are detected 40 min after injection. At that time point serum domperidone is increased 48‐fold. Most importantly, domperidone is exclusively detectable in high amounts in the brain of PolyDOM injected mice and not in mice injected with bare domperidone.
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Back Cover: A D‐Peptide Ligand of Nicotine Acetylcholine Receptors for Brain‐Targeted Drug Delivery (Angew. Chem. Int. Ed. 10/2015) 下载免费PDF全文
Xiaoli Wei Dr. Changyou Zhan Qing Shen Prof. Wei Fu Cao Xie Jie Gao Chunmei Peng Prof. Ping Zheng Prof. Weiyue Lu 《Angewandte Chemie (International ed. in English)》2015,54(10):3152-3152
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Jun Yue Shi Liu Rui Wang Xiuli Hu Zhigang Xie Yubin Huang Xiabin Jing 《Macromolecular bioscience》2012,12(9):1209-1219
Multifunctional hybrid micelles are prepared from amphiphilic mal‐PEG‐b‐PLA and mPEG‐b‐P(LA‐co‐DHC/RhB) block copolymers. A specific anti‐transferrin receptor antibody, OX26, is linked onto the surface of the micelles. ELISA indicates that the conjugated antibody preserves its activity. OX26 conjugation can increase the uptake efficiency of micelles by target cell lines (C6). Pharmacokinetics and in vivo biodistribution experiments are carried out to investigate the ability of OX26‐conjugated micelles (immunomicelles) to cross the blood–brain barrier. The data show that the brain uptake of OX26‐conjugated micelles is much more than that of OX26‐free ones. Therefore, OX26‐conjugated micelles will be promising drug carriers to cross the blood‐brain barrier.
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Fan Xiao Lin Lin Zhicong Chao Chen Shao Zhe Chen Zixiang Wei Jingxiong Lu Yishun Huang Lanqing Li Quan Liu Yongye Liang Leilei Tian 《Angewandte Chemie (International ed. in English)》2020,59(24):9702-9710
DNA nanotechnology plays an increasingly important role in the biomedical field; however, its application in the design of organic nanomaterials is underexplored. Herein, we report the use of DNA nanotechnology to transport a NIR‐II‐emitting nanofluorophore across the blood–brain barrier (BBB), facilitating non‐invasive imaging of brain tumors. Specifically, the DNA block copolymer, PS‐b‐DNA, is synthesized through a solid‐phase click reaction. We demonstrate that its self‐assembled structure shows exceptional cluster effects, among which BBB‐crossing is the most notable. Therefore, PS‐b‐DNA is utilized as an amphiphilic matrix to fabricate a NIR‐II nanofluorephore, which is applied in in vivo bioimaging. Accordingly, the NIR‐II fluorescence signal of the DNA‐based nanofluorophore localized at a glioblastoma is 3.8‐fold higher than the NIR‐II fluorescence signal of the PEG‐based counterpart. The notably increased imaging resolution will significantly benefit the further diagnosis and therapy of brain tumors. 相似文献
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Chenmala Karthika Agnieszka Najda Joanna Klepacka Mehrukh Zehravi Rokeya Akter Muhammad Furqan Akhtar Ammara Saleem Majed Al-Shaeri Banani Mondal Ghulam Md. Ashraf Priti Tagde Sarker Ramproshad Zubair Ahmad Farhat S. Khan Md. Habibur Rahman 《Molecules (Basel, Switzerland)》2022,27(14)
A brain tumor (BT) is a condition in which there is growth or uncontrolled development of the brain cells, which usually goes unrecognized or is diagnosed at the later stages. Since the mechanism behind BT is not clear, and the various physiological conditions are difficult to diagnose, the success rate of BT is not very high. This is the central issue faced during drug development and clinical trials with almost all types of neurodegenerative disorders. In the first part of this review, we focus on the concept of brain tumors, their barriers, and the types of delivery possible to target the brain cells. Although various treatment methods are available, they all have side effects or toxic effects. Hence, in the second part, a correlation was made between the use of resveratrol, a potent antioxidant, and its advantages for brain diseases. The relationship between brain disease and the blood–brain barrier, multi-drug resistance, and the use of nanomedicine for treating brain disorders is also mentioned. In short, a hypothetical concept is given with a background investigation into the use of combination therapy with resveratrol as an active ingredient, the possible drug delivery, and its formulation-based approach. 相似文献
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Simon Giret Christophe Théron Audrey Gallud Dr. Marie Maynadier Dr. Magali Gary‐Bobo Dr. Marcel Garcia Dr. Michel Wong Chi Man Dr. Carole Carcel 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(38):12806-12814
Two new prodrugs, bearing two and three 5‐fluorouracil (5‐FU) units, respectively, have been synthesized and were shown to efficiently treat human breast cancer cells. In addition to 5‐FU, they were intended to form complexes through H‐bonds to an organo‐bridged silane prior to hydrolysis‐condensation through sol–gel processes to construct acid‐responsive bridged silsesquioxanes (BS). Whereas 5‐FU itself and the prodrug bearing two 5‐FU units completely leached out from the corresponding materials, the prodrug bearing three 5‐FU units was successfully maintained in the resulting BS. Solid‐state NMR (29Si and 13C) spectroscopy show that the organic fragments of the organo‐bridged silane are retained in the hybrid through covalent bonding and the 1H NMR spectroscopic analysis provides evidence for the hydrogen‐bonding interactions between the prodrug bearing three 5‐FU units and the triazine‐based hybrid matrix. The complex in the BS is not affected under neutral medium and operates under acidic conditions even under pH as high as 5 to deliver the drug as demonstrated by HPLC analysis and confirmed by FTIR and 13C NMR spectroscopic studies. Such functional BS are promising materials as carriers to avoid the side effects of the anticancer drug 5‐FU thanks to a controlled and targeted drug delivery. 相似文献
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Xiao‐Gang Wang Lei Xu Min‐Jie Li Xian‐Zheng Zhang 《Angewandte Chemie (International ed. in English)》2020,59(41):18078-18086
Multi‐component MOFs contain multiple sets of unique and hierarchical pores, with different functions for different applications, distributed in their inter‐linked domains. Herein, we report the construction of a class of precisely aligned flexible‐on‐rigid hybrid‐phase MOFs with a unique rods‐on‐octahedron morphology. We demonstrated that hybrid‐phase MOFs can be constructed based on two prerequisites: the partially matched topology at the interface of the two frameworks, and the structural flexibility of MOFs with acs topology, which can compensate for the differences in lattice parameters. Furthermore, we achieved domain selective loading of multiple guest molecules into the hybrid‐phase MOF, as observed by scanning transmission electron microscopy–energy‐dispersive X‐ray spectrometry elemental mapping. Most importantly, we successfully applied the constructed hybrid‐phase MOF to develop a dual‐drug delivery system with controllable loading ratio and release kinetics. 相似文献
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Nicoletta di Leo Stefania Moscato Marco Borso Simona Sestito Beatrice Polini Lavinia Bandini Agostina Grillone Matteo Battaglini Alessandro Saba Letizia Mattii Gianni Ciofani Grazia Chiellini 《Molecules (Basel, Switzerland)》2021,26(6)
Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1). Currently, several research groups are investigating the pharmacological effects of T1AM systemic administration in the search of novel therapeutic approaches for the treatment of interlinked pathologies, such as metabolic and neurodegenerative diseases (NDDs). A critical aspect in the development of new drugs for NDDs is to know their distribution in the brain, which is fundamentally related to their ability to cross the blood–brain barrier (BBB). To this end, in the present study we used the immortalized mouse brain endothelial cell line bEnd.3 to develop an in vitro model of BBB and evaluate T1AM and TA1 permeability. Both drugs, administered at 1 µM dose, were assayed by high-performance liquid chromatography coupled to mass spectrometry. Our results indicate that T1AM is able to efficiently cross the BBB, whereas TA1 is almost completely devoid of this property. 相似文献
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Metal–Organic‐Framework‐Templated Polyelectrolyte Nanocapsules for the Encapsulation and Delivery of Small‐Molecule–Polymer Conjugates 下载免费PDF全文
Shuo Liu Jianbin Chen Xiaojia Bao Tao Li Yunyang Ling Chunxiang Li Prof. Dr. Chuanliu Wu Prof. Dr. Yibing Zhao 《化学:亚洲杂志》2016,11(12):1811-1820
Herein, we report a strategy for exploiting nanoscale metal–organic frameworks (nano‐MOFs) as templates for the layer‐by‐layer (LbL) assembly of polyelectrolytes. Because small‐molecule drugs or imaging agents cannot be efficiently encapsulated by polyelectrolyte nanocapsules, we investigated two promising and biocompatible polymers (comb‐shaped polyethylene glycol (PEG) and hyperbranched polyglycerol‐based PEG) for the conjugation of model drugs and imaging agents, which were then encapsulated inside the nano‐MOF‐templated nanocapsules. Furthermore, we also systemically explored the release kinetics of the encapsulated conjugates, and examined how the encapsulation and/or release processes could be controlled by varying the composition and architecture of the polymers. We envision that our nano‐MOFs‐templated nanocapsules, through combining with small‐molecule–polymer conjugates, will represent a new type of delivery system that could open up new opportunities for biomedical applications. 相似文献
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Pengfei Xu Yonggui Song Bingwei Feng Qiang Zeng Baixi Shan Kuangyi Liu Dan Su 《Biomedical chromatography : BMC》2019,33(1)
Keke capsule as a traditional Chinese medicine formulation is used to relieve cough, for analgesia and to reduce bronchial asthma. The multi‐components are absorbed into the blood and brain after oral administration of Keke capsule, with no systematic investigation so far. A reliable and rapid UPLC–QTOF–MSE combined with a data processing software platform was used to characterize the components of Keke capsule and simultaneously identify bioactive components in blood and brain tissues in rat after oral administration. Consequently, a total of 41 components of Keke capsule, including alkaloids, flavone, flavonols, triterpene, lignanoid, organic acids, glycosides and coumarin were identified. Twenty‐one components were found in plasma, including 18 prototypes and three metabolites; 15 components were found in brain tissues, including 10 prototypes and five metabolites. Alkaloids and flavonoids in Keke capsule were the main components which were absorbed into blood. The main alkaloids of Keke capsule can pass through the blood–brain barrier and show different distribution tendencies in brain tissues. The main components of keke capsule was simultaneously analyzed by throughput analysis, and the corresponding bioactive components were examined by blood‐brain barrier in the rat after oral administration of the capsule. 相似文献
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Isabel Abnades Lzaro Connor J. R. Wells Ross S. Forgan 《Angewandte Chemie (International ed. in English)》2020,59(13):5211-5217
Metal–organic frameworks (MOFs) are emerging as leading candidates for nanoscale drug delivery, as a consequence of their high drug capacities, ease of functionality, and the ability to carefully engineer key physical properties. Despite many anticancer treatment regimens consisting of a cocktail of different drugs, examples of delivery of multiple drugs from one MOF are rare, potentially hampered by difficulties in postsynthetic loading of more than one cargo molecule. Herein, we report a new strategy, multivariate modulation, which allows incorporation of up to three drugs in the Zr MOF UiO‐66 by defect‐loading. The drugs are added to one‐pot solvothermal synthesis and are distributed throughout the MOF at defect sites by coordination to the metal clusters. This tight binding comes with retention of crystallinity and porosity, allowing a fourth drug to be postsynthetically loaded into the MOFs to yield nanoparticles loaded with cocktails of drugs that show enhancements in selective anticancer cytotoxicity against MCF‐7 breast cancer cells in vitro. We believe that multivariate modulation is a significant advance in the application of MOFs in biomedicine, and anticipate the protocol will also be adopted in other areas of MOF chemistry, to easily produce defective MOFs with arrays of highly functionalised pores for potential application in gas separations and catalysis. 相似文献