Bioconjugate Chemistry Bioconjugate最新文献

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Synthetic Amine Linkers for Efficient Sortagging. 用于高效分类的合成胺连接体。
IF 4 2区 化学
Bioconjugate Chemistry Bioconjugate Pub Date : 2024-07-12 DOI: 10.1021/acs.bioconjchem.4c00143
Tetiana Bondarchuk, Diana Vaskiv, Elena Zhuravel, Oleh Shyshlyk, Yevhenii Hrynyshyn, Oleksandr Nedialko, Oleksandr Pokholenko, Alla Pohribna, Olga Kuchuk, Volodymyr Brovarets, Sergey Zozulya
{"title":"Synthetic Amine Linkers for Efficient Sortagging.","authors":"Tetiana Bondarchuk, Diana Vaskiv, Elena Zhuravel, Oleh Shyshlyk, Yevhenii Hrynyshyn, Oleksandr Nedialko, Oleksandr Pokholenko, Alla Pohribna, Olga Kuchuk, Volodymyr Brovarets, Sergey Zozulya","doi":"10.1021/acs.bioconjchem.4c00143","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00143","url":null,"abstract":"<p><p>Enzymatic site-specific bioconjugation techniques, in particular sortase-mediated ligation, are increasingly used to generate conjugated proteins for a wide array of applications. Extension of the utility and practicality of sortagging for diverse purposes is critically dependent on further improvement of the efficiency of sortagging reactions with a wider structural variety of substrates. We present a comprehensive comparative mass spectrometry screening study of synthetic nonpeptidic incoming amine nucleophile substrates of <i>Staphylococcus aureus</i> Sortase A enzyme. We have identified the optimal structural motifs among the chemically diverse set of 452 model primary and secondary amine-containing sortagging substrates, and we demonstrate the utility of representative amine linkers for efficient C-terminal biotinylation of nanobodies.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lignin-Based Nanoparticles for Combination of Tumor Oxidative Stress Amplification and Reactive Oxygen Species Responsive Drug Release. 木质素基纳米颗粒结合肿瘤氧化应激放大和活性氧反应药物释放。
IF 4 2区 化学
Bioconjugate Chemistry Bioconjugate Pub Date : 2024-07-11 DOI: 10.1021/acs.bioconjchem.4c00261
Ziwei Zhou, Jin Wang, Xin Xu, Zhuang Wang, Lingchen Mao, Shanhu Zhang, Huanhuan Zhang, Yuqiang Li, Qingsong Yu, Ni Jiang, Guan Zhang, Zhihua Gan, Zhenbo Ning
{"title":"Lignin-Based Nanoparticles for Combination of Tumor Oxidative Stress Amplification and Reactive Oxygen Species Responsive Drug Release.","authors":"Ziwei Zhou, Jin Wang, Xin Xu, Zhuang Wang, Lingchen Mao, Shanhu Zhang, Huanhuan Zhang, Yuqiang Li, Qingsong Yu, Ni Jiang, Guan Zhang, Zhihua Gan, Zhenbo Ning","doi":"10.1021/acs.bioconjchem.4c00261","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00261","url":null,"abstract":"<p><p>In this study, maleic anhydride-modified lignin (LG-M), a ROS-cleavable thioketal (TK) bond, and polyethylene glycol (PEG) were used to synthesize a lignin-based copolymer (LG-M(TK)-PEG). Doxorubicin (DOX) was attached to the ROS-cleavable bond in the LG-M(TK)-PEG for the preparation of the ROS-activatable DOX prodrug (LG-M(TK-DOX)-PEG). Nanoparticles (NPs) with a size of 125.7 ± 3.1 nm were prepared by using LG-M(TK-DOX)-PEG, and they exhibited enhanced uptake by cancer cells compared to free DOX. Notably, the presence of lignin in the nanoparticles could boost ROS production in breast cancer 4T1 cells while showing little effect on L929 normal cells. This selective effect facilitated the specific activation of the DOX prodrug in the tumor microenvironment, resulting in the superior tumor inhibitory effects and enhanced biosafety relative to free DOX. This work demonstrates the potential of the LG-M(TK-DOX)-PEG NPs as an efficient drug delivery system for cancer treatment.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeted Protein Degradation (TPD) for Immunotherapy: Understanding Proteolysis Targeting Chimera-Driven Ubiquitin-Proteasome Interactions. 用于免疫疗法的靶向蛋白质降解(TPD):了解针对嵌合体驱动的泛素-蛋白酶体相互作用的蛋白质分解。
IF 4 2区 化学
Bioconjugate Chemistry Bioconjugate Pub Date : 2024-07-11 DOI: 10.1021/acs.bioconjchem.4c00253
Rajamanikkam Kamaraj, Subhrojyoti Ghosh, Souvadra Das, Shinjini Sen, Priyanka Kumar, Madhurima Majumdar, Renesa Dasgupta, Sampurna Mukherjee, Shrimanti Das, Indrilla Ghose, Petr Pavek, Muruga Poopathi Raja Karuppiah, Anil A Chuturgoon, Krishnan Anand
{"title":"Targeted Protein Degradation (TPD) for Immunotherapy: Understanding Proteolysis Targeting Chimera-Driven Ubiquitin-Proteasome Interactions.","authors":"Rajamanikkam Kamaraj, Subhrojyoti Ghosh, Souvadra Das, Shinjini Sen, Priyanka Kumar, Madhurima Majumdar, Renesa Dasgupta, Sampurna Mukherjee, Shrimanti Das, Indrilla Ghose, Petr Pavek, Muruga Poopathi Raja Karuppiah, Anil A Chuturgoon, Krishnan Anand","doi":"10.1021/acs.bioconjchem.4c00253","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00253","url":null,"abstract":"<p><p>Targeted protein degradation or TPD, is rapidly emerging as a treatment that utilizes small molecules to degrade proteins that cause diseases. TPD allows for the selective removal of disease-causing proteins, including proteasome-mediated degradation, lysosome-mediated degradation, and autophagy-mediated degradation. This approach has shown great promise in preclinical studies and is now being translated to treat numerous diseases, including neurodegenerative diseases, infectious diseases, and cancer. This review discusses the latest advances in TPD and its potential as a new chemical modality for immunotherapy, with a special focus on the innovative applications and cutting-edge research of PROTACs (Proteolysis TArgeting Chimeras) and their efficient translation from scientific discovery to technological achievements. Our review also addresses the significant obstacles and potential prospects in this domain, while also offering insights into the future of TPD for immunotherapeutic applications.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microwave-Assisted Synthesis of β-N-Aryl Glycoamphiphiles with Diverse Supramolecular Assemblies and Lectin Accessibility. 微波辅助合成β-N-芳基糖脂酰胺,具有多种超分子结构和连接蛋白可及性。
IF 4 2区 化学
Bioconjugate Chemistry Bioconjugate Pub Date : 2024-07-10 DOI: 10.1021/acs.bioconjchem.4c00224
Aïcha Abdallah, Emilie Gillon, Patrice Rannou, Anne Imberty, Sami Halila
{"title":"Microwave-Assisted Synthesis of β-<i>N</i>-Aryl Glycoamphiphiles with Diverse Supramolecular Assemblies and Lectin Accessibility.","authors":"Aïcha Abdallah, Emilie Gillon, Patrice Rannou, Anne Imberty, Sami Halila","doi":"10.1021/acs.bioconjchem.4c00224","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00224","url":null,"abstract":"<p><p>Glycoamphiphiles have attracted considerable interest in a broad range of application fields owing to their solution and bulk-state self-assembly abilities. Despite their importance, the straightforward synthesis of glycoamphiphiles consisting of a hydrophilic carbohydrate linked to a hydrophobic aglycone remains one of the major challenges in glycosciences. Here, a rapid, simple, and efficient synthetic access to chemically stable glycoamphiphiles at physiological pH, namely, <i>N</i>-(β-d-glycosyl)-2-alkylbenzamide, is reported. It leverages the nonreductive amination of unprotected carbohydrates with <i>ortho</i>-substituted aniline derivatives which could be readily obtained by reacting commercially available primary alkylamines with isatoic anhydride. This strategy avoids protection and deprotection of sugar hydroxyl groups and the use of reductive agents, which makes it advantageous in terms of atom and step economy. Moreover, in order to circumvent the cons of classical <i>N</i>-aryl glycosylation, we investigate the use of microwave as a heat source that provides fast, clean, and high-yield β-<i>N</i>-arylation of unprotected carbohydrates. Their self-assembly into water led to multiple morphologies of dynamic supramolecular glycoamphiphiles that were characterized to assess their ability to bind to lectins from pathogenic bacteria. Biophysical interactions probed by isothermal titration microcalorimetry revealed micromolar affinities for most of the synthesized glycoamphiphiles.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
AUNP-12 Near-Infrared Fluorescence Probes across NIR-I to NIR-II Enable In Vivo Detection of PD-1/PD-L1 Axis in the Tumor Microenvironment. AUNP-12 近红外荧光探针跨越近红外-I 到近红外-II,可在体内检测肿瘤微环境中的 PD-1/PD-L1 轴。
IF 4 2区 化学
Bioconjugate Chemistry Bioconjugate Pub Date : 2024-07-09 DOI: 10.1021/acs.bioconjchem.4c00266
Xinyu Zhang, Ping Wang, Guangyuan Shi, Chu Tang, Huadan Xue
{"title":"AUNP-12 Near-Infrared Fluorescence Probes across NIR-I to NIR-II Enable <i>In Vivo</i> Detection of PD-1/PD-L1 Axis in the Tumor Microenvironment.","authors":"Xinyu Zhang, Ping Wang, Guangyuan Shi, Chu Tang, Huadan Xue","doi":"10.1021/acs.bioconjchem.4c00266","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00266","url":null,"abstract":"<p><p>The innovative PD-1/PD-L1 pathway strategy is gaining significant traction in cancer therapeutics. However, fluctuating response rates of 20-40% to PD-1/PD-L1 inhibitors, coupled with the risk of hyperprogression after immunotherapy, underscore the need for accurate patient selection and the identification of more beneficiaries. Molecular imaging, specifically near-infrared (NIR) fluorescence imaging, is a valuable alternative for real-time, noninvasive visualization of dynamic PD-L1 expression <i>in vivo</i>. This research introduces AUNP-12, a novel PD-L1-targeting peptide antagonist conjugated with Cy5.5 and CH1055 for first (NIR-I) and second near-infrared (NIR-II) imaging. These probes have proven to be effective in mapping PD-L1 expression across various mouse tumor models, offering insights into tumor-immune interactions. This study highlights the potential of AUNP-12-Cy5.5 and AUNP-12-CH1055 for guiding clinical immunotherapy through precise patient stratification and dynamic monitoring, supporting the shift toward molecular imaging for personalized cancer care.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rational Design of Cyanine-Based Fluorogenic Dimers to Reduce Nonspecific Interactions with Albumin and Lipid Bilayers: Application to Highly Sensitive Imaging of GPCRs in Living Cells. 减少与白蛋白和脂质双分子层的非特异性相互作用的氰基荧光二聚体的合理设计:应用于活细胞中 GPCR 的高灵敏度成像。
IF 4 2区 化学
Bioconjugate Chemistry Bioconjugate Pub Date : 2024-07-09 DOI: 10.1021/acs.bioconjchem.4c00147
Yann Berthomé, Julie Gerber, Fabien Hanser, Stéphanie Riché, Nicolas Humbert, Christel Valencia, Pascal Villa, Julie Karpenko, Océane Florès, Dominique Bonnet
{"title":"Rational Design of Cyanine-Based Fluorogenic Dimers to Reduce Nonspecific Interactions with Albumin and Lipid Bilayers: Application to Highly Sensitive Imaging of GPCRs in Living Cells.","authors":"Yann Berthomé, Julie Gerber, Fabien Hanser, Stéphanie Riché, Nicolas Humbert, Christel Valencia, Pascal Villa, Julie Karpenko, Océane Florès, Dominique Bonnet","doi":"10.1021/acs.bioconjchem.4c00147","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00147","url":null,"abstract":"<p><p>Fluorogenic dimers with polarity-sensitive folding are powerful probes for live-cell bioimaging. They switch on their fluorescence only after interacting with their targets, thus leading to a high signal-to-noise ratio in wash-free bioimaging. We previously reported the first near-infrared fluorogenic dimers derived from cyanine 5.5 dyes for the optical detection of G protein-coupled receptors. Owing to their hydrophobic character, these dimers are prone to form nonspecific interactions with proteins such as albumin and with the lipid bilayer of the cell membrane resulting in a residual background fluorescence in complex biological media. Herein, we report the rational design of new fluorogenic dimers derived from cyanine 5. By modulating the chemical structure of the cyanine units, we discovered that the two asymmetric cyanine 5.25 dyes were able to form intramolecular H-aggregates and self-quenched in aqueous media. Moreover, the resulting original dimeric probes enabled a significant reduction of the nonspecific interactions with bovine serum albumin and lipid bilayers compared with the first generation of cyanine 5.5 dimers. Finally, the optimized asymmetric fluorogenic dimer was grafted to carbetocin for the specific imaging of the oxytocin receptor under no-wash conditions directly in cell culture media, notably improving the signal-to-background ratio compared with the previous generation of cyanine 5.5 dimers.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Permutational Encoding Strategy Accelerates HIT Validation from Single-Stranded DNA-Encoded Libraries. 排列编码策略加速了单链 DNA 编码库的 HIT 验证。
IF 4 2区 化学
Bioconjugate Chemistry Bioconjugate Pub Date : 2024-07-04 DOI: 10.1021/acs.bioconjchem.4c00233
Sara Puglioli, Mosè Fabbri, Claudia Comacchio, Laura Alvigini, Roberto De Luca, Sebastian Oehler, Ettore Gilardoni, Gabriele Bassi, Samuele Cazzamalli, Dario Neri, Nicholas Favalli
{"title":"Permutational Encoding Strategy Accelerates HIT Validation from Single-Stranded DNA-Encoded Libraries.","authors":"Sara Puglioli, Mosè Fabbri, Claudia Comacchio, Laura Alvigini, Roberto De Luca, Sebastian Oehler, Ettore Gilardoni, Gabriele Bassi, Samuele Cazzamalli, Dario Neri, Nicholas Favalli","doi":"10.1021/acs.bioconjchem.4c00233","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00233","url":null,"abstract":"<p><p>DNA-Encoded Libraries (DELs) allow the parallel screening of millions of compounds for various applications, including <i>de novo</i> discovery or affinity maturation campaigns. However, library construction and HIT resynthesis can be cumbersome, especially when library members present an unknown stereochemistry. We introduce a permutational encoding strategy suitable for the construction of highly pure single-stranded single-pharmacophore DELs, designed to distinguish isomers at the sequencing level (e.g., stereoisomers, regio-isomers, and peptide sequences). This approach was validated by synthesizing a mock 921,600-member 4-amino-proline single-stranded DEL (\"<b>DEL1</b>\"). While screening <b>DEL1</b> against different targets, high-throughput sequencing results showed selective enrichment of the most potent stereoisomers, with enrichment factors that outperform conventional encoding strategies. The versatility of our methodology was additionally validated by encoding 24 scaffolds derived from different permutations of the amino acid sequence of a previously described cyclic peptide targeting Fibroblast Activation Protein (FAP-2286). The resulting library (\"<b>DEL2</b>\") was interrogated against human FAP, showing selective enrichment of five cyclic peptides. We observed a direct correlation between enrichment factors and on-DNA binding affinities. The presented encoding methodology accelerates drug discovery by facilitating library synthesis and streamlining HIT resynthesis while enhancing enrichment factors at the DEL sequencing level. This facilitates the identification of HIT candidates prior to medicinal chemistry and affinity maturation campaigns.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Photoinduced Charge Centralization Quenches the Fluorescence of Conjugation-Fused Tetrazine Labels with Red-to-Near-Infrared Emissions. 光诱导电荷集中可淬灭共轭融合四嗪标签的荧光,使其从红光到近红外发射。
IF 4 2区 化学
Bioconjugate Chemistry Bioconjugate Pub Date : 2024-07-04 DOI: 10.1021/acs.bioconjchem.4c00227
Tianruo Shen, Xiaogang Liu
{"title":"Photoinduced Charge Centralization Quenches the Fluorescence of Conjugation-Fused Tetrazine Labels with Red-to-Near-Infrared Emissions.","authors":"Tianruo Shen, Xiaogang Liu","doi":"10.1021/acs.bioconjchem.4c00227","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00227","url":null,"abstract":"<p><p>Tetrazine-derived fluorogenic labels are extensively studied for their potential in biological and medical imaging. Nonetheless, the fluorescence quenching mechanism in numerous precursors continues to be debated, particularly as the wavelengths extend into the red and near-infrared (NIR) regions. This challenge poses obstacles to systematically optimizing their fluorogenicity, i.e., achieving red-shifted wavelengths and improved fluorescence turn-on signals through click reactions. This paper highlights the significance of photoinduced charge centralization (PCC), a quenching mechanism observed in tetrazine-fused fluorogenic labels with integrated π-conjugations. PCC is primarily responsible for the quenching effects observed in such labels emitting in the red-to-NIR spectrum. Drawing from structure-property relationships, this study proposes two molecular design strategies that incorporate the PCC mechanism and constitutional isomerization to develop high-performance tetrazine-based labels. These strategies facilitate multiplex fluorescence imaging following click reactions, promising significant advancements in bio-orthogonal imaging techniques.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Size-Dependent Glioblastoma Targeting by Polymeric Nanoruler with Prolonged Blood Circulation. 可延长血液循环的聚合物纳米载体对胶质母细胞瘤的大小依赖性靶向作用
IF 4 2区 化学
Bioconjugate Chemistry Bioconjugate Pub Date : 2024-07-03 DOI: 10.1021/acs.bioconjchem.4c00235
Yukine Ishibashi, Mitsuru Naito, Yusuke Watanuki, Mao Hori, Satomi Ogura, Kaori Taniwaki, Masaru Cho, Ryosuke Komiya, Yuki Mochida, Kanjiro Miyata
{"title":"Size-Dependent Glioblastoma Targeting by Polymeric Nanoruler with Prolonged Blood Circulation.","authors":"Yukine Ishibashi, Mitsuru Naito, Yusuke Watanuki, Mao Hori, Satomi Ogura, Kaori Taniwaki, Masaru Cho, Ryosuke Komiya, Yuki Mochida, Kanjiro Miyata","doi":"10.1021/acs.bioconjchem.4c00235","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00235","url":null,"abstract":"<p><p>Currently, there is no effective treatment for glioblastoma multiforme (GBM), the most frequent and malignant type of brain tumor. The blood-brain (tumor) barrier (BB(T)B), which is composed of tightly connected endothelial cells and pericytes (with partial vasculature collapse), hampers nanomedicine accumulation in tumor tissues. We aimed to explore the effect of nanomedicine size on passive targeting of GBM. A series of size-tunable poly(ethylene glycol) (PEG)-grafted copolymers (gPEGs) were constructed with hydrodynamic diameters of 8-30 nm. Biodistribution studies using orthotopic brain tumor-bearing mice revealed that gPEG brain tumor accumulation was maximized at 10 nm with ∼14 dose %/g of tumor, which was 19 times higher than that in the normal brain region and 4.2 times higher than that of 30-nm gPEG. Notably, 10-nm gPEG exhibited substantially higher brain tumor accumulation than 11-nm linear PEG owing to the prolonged blood circulation property of gPEGs, which is derived from a densely PEG-packed structure. 10 nm gPEG exhibited deeper penetration into the brain tumor tissue than the larger gPEGs did (>10 nm). This study demonstrates, for the first time, the great potential of a nanomedicine downsizing strategy for passive GBM targeting.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synthesis, Characterization, and Potential Usefulness in Liver Function Assessment of Novel Bile Acid Derivatives with Near-Infrared Fluorescence (NIRBAD). 新型近红外荧光胆汁酸衍生物 (NIRBAD) 的合成、表征及其在肝功能评估中的潜在用途。
IF 4 2区 化学
Bioconjugate Chemistry Bioconjugate Pub Date : 2024-07-03 DOI: 10.1021/acs.bioconjchem.4c00168
Alvaro G Temprano, Beatriz Sanchez de Blas, Concepción Pérez-Melero, Ricardo Espinosa-Escudero, Oscar Briz, Paula Cinca-Fernando, Lucia Llera, Maria J Monte, Francisco A Bermejo-Gonzalez, Jose J G Marin, Marta R Romero
{"title":"Synthesis, Characterization, and Potential Usefulness in Liver Function Assessment of Novel Bile Acid Derivatives with Near-Infrared Fluorescence (NIRBAD).","authors":"Alvaro G Temprano, Beatriz Sanchez de Blas, Concepción Pérez-Melero, Ricardo Espinosa-Escudero, Oscar Briz, Paula Cinca-Fernando, Lucia Llera, Maria J Monte, Francisco A Bermejo-Gonzalez, Jose J G Marin, Marta R Romero","doi":"10.1021/acs.bioconjchem.4c00168","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00168","url":null,"abstract":"<p><p>Conventional serum markers often fail to accurately detect cholestasis accompanying many liver diseases. Although elevation in serum bile acid (BA) levels sensitively reflects impaired hepatobiliary function, other factors altering BA pool size and enterohepatic circulation can affect these levels. To develop fluorescent probes for extracorporeal noninvasive hepatobiliary function assessment by real-time monitoring methods, 1,3-dipolar cycloaddition reactions were used to conjugate near-infrared (NIR) fluorochromes with azide-functionalized BA derivatives (BAD). The resulting compounds (NIRBADs) were chromatographically (FC and PTLC) purified (>95%) and characterized by fluorimetry, <sup>1</sup>H NMR, and HRMS using ESI ionization coupled to quadrupole TOF mass analysis. Transport studies using CHO cells stably expressing the BA carrier NTCP were performed by flow cytometry. Extracorporeal fluorescence was detected in anesthetized rats by high-resolution imaging analysis. Three NIRBADs were synthesized by conjugating alkynocyanine 718 with cholic acid (CA) at the COOH group via an ester (NIRBAD-1) or amide (NIRBAD-3) spacer, or at the 3α-position by a triazole link (NIRBAD-2). NIRBADs were efficiently taken up by cells expressing NTCP, which was inhibited by taurocholic acid (TCA). Following i.v. administration of NIRBAD-3 to rats, liver uptake and consequent release of NIR fluorescence could be extracorporeally monitored. This transient organ-specific handling contrasted with the absence of release to the intestine of alkynocyanine 718 and the lack of hepatotropism observed with other probes, such as indocyanine green. NIRBAD-3 administration did not alter serum biomarkers of hepatic and renal toxicity. NIRBADs can serve as probes to evaluate hepatobiliary function by noninvasive extracorporeal methods.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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