Bioconjugate Chemistry最新文献

{"title":"In Vivo Imaging of Pancreatic Cancer in BALB/c Mice Using Erlotinib-Conjugated Carbon Quantum Dots Derived from 1,4,5,8-Tetraminoanthraquinone.","authors":"Susan Varghese, Merin K Abraham, Geneva Indongo, Greeshma Rajeevan, Arathy B K Kala, Aishwarya Lekshman, Sony George","doi":"10.1021/acs.bioconjchem.5c00191","DOIUrl":"10.1021/acs.bioconjchem.5c00191","url":null,"abstract":"<p><p>Pancreatic cancer remains one of the most aggressive malignancies with a poor prognosis due to late-stage diagnosis and limited treatment options. Fluorescence imaging has emerged as a valuable tool for early detection and targeted imaging of pancreatic cancer, offering improved visualization of tumors at the molecular level. Among various fluorescence techniques, fluorescence imaging using longer-wavelength nanomaterials holds significant promise due to their deeper tissue penetration and reduced background autofluorescence. In this study, we report the development of red-emitting carbon quantum dots designed for targeted imaging of pancreatic cancer. These carbon quantum dots were functionalized with erlotinib to enhance cancer cell specificity. In vitro biological evaluations demonstrated minimal cytotoxicity, prompting further investigations in vivo. Using BALB/c mice as model organisms, in vivo imaging showcased the efficacy of the developed probe for targeted pancreatic cancer detection, suggesting its potential as a robust tool for cancer diagnostics and imaging.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1329-1339"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135889","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}

{"title":"Conceptualization and Preliminary Characterization of Poloxamer-Based Hydrogels for Biomedical Applications.","authors":"Marta Tuszynska, Joanna Skopinska-Wisniewska, Mateusz Bartniak, Anna Bajek","doi":"10.1021/acs.bioconjchem.5c00030","DOIUrl":"10.1021/acs.bioconjchem.5c00030","url":null,"abstract":"<p><p>Poloxamers are widely used in biomedical applications, but their effectiveness depends on achieving an optimal sol-gel phase transition near body temperature. This study evaluates three different poloxamer mixtures for their potential in treating meniscus tears, focusing on gel formation, injectability, and cell compatibility. The rheological properties, cytotoxicity assessments, and cellular migration experiments were studied using NIH/3T3 fibroblast cells as the standard experimental model for primary research. The poloxamer hydrogels showed properties well suited to injectable or drug delivery systems. Specifically, the combination of Synperonic F108 and Poloxamer 188 tended to show less adhesion and more aggregation, followed by a greater number of viable cells, suggesting its utility as a coating or foundational matrix. Concurrently, the Kolliphor 407 and Poloxamer 188 combination exhibited increased viscosity, maintaining a gel state at physiological temperature. Its biocompatibility indicated the potential for injectable controlled-release systems for musculoskeletal injuries. Our findings demonstrate that the poloxamer concentration and composition significantly influence their biomedical applications. These triblock copolymer systems indicated useful characteristics for surgical applications, such as favorable sol-gel transition kinetics and biocompatibility, suggesting potential applications in osteoarticular regeneration.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1169-1179"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, and Biological Evaluation of a Novel Long-Acting Human Complement C3 Inhibitor Synthesized via the PASylation-Lipidation Modular (PLM) Platform.","authors":"Chengcheng Wang, Yapeng Wang, Yu Duan, Yuanzhen Dong, Haoju Hua, Huixin Cui, Shuaiyi Huang, Zongqing Huang, Jianguang Lu, Chunyong Ding, Zhengyan Cai, Jun Feng","doi":"10.1021/acs.bioconjchem.5c00108","DOIUrl":"10.1021/acs.bioconjchem.5c00108","url":null,"abstract":"<p><p>The complement system is essential for immune defense, but its dysregulation contributes to various complement-mediated disorders, including paroxysmal nocturnal hemoglobinuria (PNH). <b>CP40</b> (a cyclic peptide also known as AMY101), effectively inhibits complement activation by preventing the initial binding of the C3 substrate to convertase. Despite its potency, <b>CP40</b> has a very short plasma half-life when unbound to human C3, necessitating frequent dosing. We developed a novel PASylation-Lipidation Modular (PLM) platform. This platform incorporates a solubilizing PAS module and a half-life-extending lipid moiety into <b>CP40</b> via a chemical linker. Systematic optimization of the spacer and lipid components in PLM-modified <b>CP40</b> analogues identified <b>6C1</b> as a lead compound. Compared to <b>CP40</b>, <b>6C1</b> exhibited a 5-fold increase in antihemolytic potency in the classical complement pathway and a 6.3-fold improvement in solubility. <i>In vivo</i> studies demonstrated that PLM-<b>CP40</b> analogues possess superior pharmacokinetic properties, with a 15.6-fold extension in half-life relative to unmodified <b>CP40</b>. Mechanistic studies revealed that the PLM platform extends half-life by interacting with albumin, which serves as a circulating depot for the compound. Surface plasmon resonance analysis and hemolysis assays postalbumin incubation demonstrated that PLM modifications maintain receptor affinity by strategically positioning the albumin-binding moiety away from the peptide region, preserving its biological activity. In a clinically relevant <i>in vitro</i> model of complement-mediated hemolysis in PNH, <b>6C1</b> effectively reduced erythrocyte lysis. The PLM platform thus offers a versatile strategy for enhancing peptide therapeutics by improving solubility, extending circulation time, and increasing efficacy, broadening their therapeutic potential.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1257-1272"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951384","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}

{"title":"Novel Approaches to Label the Surface of <i>S. aureus</i> with DBCO for Click Chemistry-Mediated Deposition of Sensitive Cargo.","authors":"Tsvetelina H Baryakova, Chia-Chien Hsu, Laura Segatori, Kevin J McHugh","doi":"10.1021/acs.bioconjchem.4c00575","DOIUrl":"10.1021/acs.bioconjchem.4c00575","url":null,"abstract":"<p><p>The strain-promoted alkyne-azide cycloaddition (SPAAC) reaction can be used to modify the surface of bacteria for a variety of applications including drug delivery, biosensing, and imaging. This is usually accomplished by first installing a small azide group within the peptidoglycan and then delivering exogenous cargo (e.g., a protein or nanoparticle) modified with a cyclooctyne group, such as dibenzocyclooctyne (DBCO), for <i>in situ</i> conjugation. However, DBCO is comparatively bulky and hydrophobic, increasing the propensity of some payloads to aggregate. In this study, we sought to invert this paradigm by exploring two novel strategies for incorporating DBCO into the peptidoglycan of <i>Staphylococcus aureus</i> and compared them to an established approach using DBCO-vancomycin. We demonstrate that DBCO-modified small molecules belonging to all three classes─a sortase peptide substrate (LPETG), two d-alanine derivatives, and vancomycin─can selectively label the <i>S. aureus</i> surface to varying degrees. In contrast to DBCO-vancomycin, the DBCO-d-alanine variants do not adversely affect the growth of <i>S. aureus</i> or lead to off-target labeling or toxicity in HEK293T or RAW 264.7 cells. Finally, we show that, unlike IgG3-Fc labeled with DBCO groups, IgG3-Fc labeled with azide groups is stable (i.e., remains water-soluble) under normal storage conditions, retains its ability to bind the immune receptor CD64, and can be successfully attached to the surface of DBCO-modified <i>S. aureus</i>. We believe that the labeling strategies explored herein will expand the paradigm of specific, nontoxic SPAAC-mediated labeling of the surface of <i>S. aureus</i> and other Gram-positive bacteria, opening the door for new applications using azide-modified cargo.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1157-1168"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118376","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}

{"title":"","authors":"Yen Thi Nguyen,&nbsp;Hyuck Jin Lee* and Namdoo Kim*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.5c00088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/bcv036i006_1948095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Luke Wharton,&nbsp;Scott W. McNeil,&nbsp;Harrison Meeres,&nbsp;Diduo Zhang,&nbsp;Aidan Ingham,&nbsp;Helen Merkens,&nbsp;Maryam Osooly,&nbsp;Cristina Rodríguez-Rodríguez,&nbsp;François Bénard and Hua Yang*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.5c00129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimeric Conjugates Using Engineered Peptide Scaffolds for Efficient siRNA Delivery.","authors":"Quentin Vicentini, Dennis Hekman, Deepak Bhatt, Rouven Stulz, Mahya Dezfouli, Peter Gennemark, Nicola Guzzi, Naoko Toki, Bojana Lazovic, Carolina Tängemo, Shalini Andersson, Samir El Andaloussi, Anders Dahlén","doi":"10.1021/acs.bioconjchem.5c00156","DOIUrl":"10.1021/acs.bioconjchem.5c00156","url":null,"abstract":"<p><p>Oligonucleotide therapeutics (ONT) traditionally involve a single targeting moiety per oligonucleotide when conjugated for organ delivery. Multimerization represents a novel approach by connecting multiple ONTs to a single scaffold, thereby influencing the drug's activity and biophysical properties <i>in vivo</i>. Recently, others have demonstrated the efficacy of this strategy, showing enhanced tissue retention and extended silencing with the capability to target multiple genes simultaneously. The investigation of diverse multimeric designs is thus an exciting opportunity to explore the delivery of the ONT. In this study, we engineered a versatile peptide branching unit able to link up to four small interfering RNAs together. We conjugated a GalNAc targeting moiety to these scaffolds for liver hepatocyte delivery and assessed their silencing activity. Our approach was further expanded to explore different peptide architectures (linear versus cyclized) and additional functionalities, including endosomal escape domains and dual target silencing. We then evaluated the constructs via subcutaneous and intravenous (i.v.) administration in mice. Notably, the intravenous administration of multimeric siRNA GalNAc demonstrated potent silencing in the liver and significantly affected liver-to-kidney biodistribution. Our findings suggest that peptides as branching units offer a promising pathway for ONT multimerization, advancing the challenges of drug delivery.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1299-1310"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Employing the SpyTag-SpyCatcher Reaction for the Modification of Supramolecular Polymers with Functional Proteins.","authors":"Fenna W B Craenmehr, Alexander Gräwe, Victor A Veenbrink, Riccardo Bellan, Maarten Merkx, Patricia Y W Dankers","doi":"10.1021/acs.bioconjchem.5c00046","DOIUrl":"10.1021/acs.bioconjchem.5c00046","url":null,"abstract":"<p><p>Supramolecular assemblies hold great potential as biomaterials for several biomedical applications. The modification of supramolecular biomaterials is needed to achieve controlled bioactive functions. Supramolecular ureidopyrimidinone (UPy) monomers have been shown to assemble into long supramolecular polymers that can be functionalized with bioactive peptides and visualized as UPy-fibers. So far, the introduction of biological functionality has been limited to small molecules and peptides. Here, we describe a general method based on SpyTag-SpyCatcher chemistry for conjugating full-length proteins with biologically relevant functions to μm-long UPy fibers via native peptide bond formation, yielding 100% conversion in a 5:95 mol % coassembly of UPy-SpyTag with UPy-glycinamide. The conjugation of monoclonal antibodies is performed using photo-cross-linkable protein G domains. We demonstrate intact fibers and colocalization of antibodies and UPy-fibers using biophysical and imaging methods and achieve recruitment of supramolecular assemblies to the surface of mammalian cells via the EGFR-specific antibody Cetuximab. The approach introduced here represents a robust and widely applicable postassembly modification method that shows promise in the functionalization of future biomaterials.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1197-1207"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing and Characterizing the Tumor-Targeting Efficiency of an Anti-EphA2-CD11b Bispecific Antibody.","authors":"Peggy A Birikorang, Dominic M Menendez, Robert Edinger, Gary Kohanbash, W Barry Edwards","doi":"10.1021/acs.bioconjchem.5c00070","DOIUrl":"10.1021/acs.bioconjchem.5c00070","url":null,"abstract":"<p><p>Targeting molecules, such as antibodies and peptides, play a key role in the precise delivery of cytotoxic payloads to tumor sites by binding to specific tumor-associated antigens or other proteins within the tumor microenvironment. This investigation evaluates the potential therapeutic application of a bispecific antibody (BsAb), which simultaneously targets EphA2, a tumor-associated antigen, and CD11b, a protein expressed by tumor-associated macrophages and myeloid-derived suppressor cells (TAMCs). Recombinantly produced anti-EphA2-CD11b-BsAb was conjugated to a bifunctional chelator, NOTA-SCN, and then radiolabeled with copper-64 (⁶⁴Cu). The [⁶⁴Cu]Cu-NOTA-anti-EphA2-CD11b-BsAb radioimmunoconjugate was subsequently administered to HT1080-fibrosarcoma-bearing nude mice via tail vein injection. Positron Emission Tomography (PET) and ex vivo biodistribution analyses were performed to determine tumor uptake and pharmacokinetic localization. At 4, 24, and 48 h postinjection (p.i.), the percent injected dose per gram (%ID/g) of [⁶⁴Cu]Cu-NOTA-anti-EphA2-CD11b-BsAb in HT1080 xenografts were 5.35 ± 2.24, 4.44 ± 1.90, and 4.10 ± 0.60, respectively. There was high uptake in the liver as well as in CD11b-expressing organs, including the spleen, bone marrow, and lung. Binding in these CD11b-rich organs was significantly reduced by coadministering the dose with nonradiolabeled anti-CD11b-IgG and anti-EphA2-CD11b-BsAb, with a concurrent increase in tumor uptake compared to nonblocked mice (8.39 ± 1.37%ID/g for blocked and 4.44 ± 1.90%ID/g for nonblocked at 24 h p.i., <i>p</i> = 0.0175). Further optimization studies showed that at lower molar activity (3.7 MBq/nmol, 100 μCi/nmol), there were significantly higher tumor accumulations and reduced uptake in CD11b-expressing organs compared to higher molar activity (22.2 MBq/nmol, 600 μCi/nmol). Anti-EphA2-CD11b-BsAb is a functional targeting molecule and would require optimization through molar activity or blocking with nonradiolabeled antibody to maximize tumor targeting.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1208-1217"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}