Bioconjugate ChemistryPub Date : 2025-05-21Epub Date: 2025-05-02DOI: 10.1021/acs.bioconjchem.4c00530
Linhui Lv, Ke Qu
{"title":"Transduction of Glycan-Lectin Binding via an Impedimetric Sensor for Glycoprotein Detection.","authors":"Linhui Lv, Ke Qu","doi":"10.1021/acs.bioconjchem.4c00530","DOIUrl":"10.1021/acs.bioconjchem.4c00530","url":null,"abstract":"<p><p>Glycoproteins are produced by glycosylation modification of proteins, and a number of glycoproteins have served as important tumor biomarkers in clinical application. Alpha-fetoprotein (AFP) is one of the representative glycoproteins that has been employed as a useful predictive and prognostic biomarker for hepatocellular carcinoma. Human AFP has an <i>N</i>-glycan portion at the asparagine residue, which includes four <i>N</i>-acetyl-glucosamine and three mannoses. In this work, building upon lectin-glycan interactions, one type of facile and capable impedimetric biosensor was fabricated utilizing microwave-prepared NH<sub>2</sub>-MIL-101(Fe) to decorate lectins as a recognition element. Two different lectins of wheat-germ agglutinin (WGA) and concanavalin A (Con A) were employed to target the <i>N</i>-acetyl-glucosamine and mannose of <i>N</i>-glycan in AFP, respectively. This work has not only accomplished the sensitive impedimetric biosensing of the AFP tumor marker (with the limit of detection down to 0.5 pg/mL and linear concentration spanning 5 orders of magnitude from 10<sup>-2</sup> to 10<sup>3</sup> ng/mL) but also replied on two kinds of lectins to \"read\" the sugar chain, transducing the minor difference of this process to impedimetric signals for display. The impedimetric data shed some light on the local microenvironment of the lectin-glycan binding event, providing some electrochemical experimental support for the biantennary structure of <i>N</i>-glycan in AFP. The mannoses were \"buried\" in the interior core of the whole <i>N</i>-glycan, increasing steric hindrance for Con A to approach and thus rendering the WGA@MIL-101(Fe)-based biosensor more superior sensing responses.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"936-944"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955921","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}
Bioconjugate ChemistryPub Date : 2025-05-21Epub Date: 2025-04-08DOI: 10.1021/acs.bioconjchem.5c00116
Yanchen Li, Jin Wang, Tingting Liu, Junyu Zhang, Yuanyuan Shan, Jie Zhang
{"title":"Discovery of a Novel ADC for Multifunctional Theranostics: From Vascular Normalization to Synergistic Therapy.","authors":"Yanchen Li, Jin Wang, Tingting Liu, Junyu Zhang, Yuanyuan Shan, Jie Zhang","doi":"10.1021/acs.bioconjchem.5c00116","DOIUrl":"10.1021/acs.bioconjchem.5c00116","url":null,"abstract":"<p><p>Previous studies have shown the potential of bevacizumab-based ADCs in tumor vascular normalization and chemotherapy synergies. Here, in order to improve the tumor treatment efficiency of ADC and further avoid drug resistance, we introduced the previously discovered photodynamic therapy group PDT into bevacizumab, which has high reactive oxygen generation efficiency and deep tissue penetration ability, and has surprising imaging effect on solid tumors. At the same time, doxorubicin, a chemotherapy drug molecule with strong cytotoxicity, has also been introduced to construct novel multifunctional integrated antibody-drug conjugates, Bevacizumab-DOX-PDT. It is proved that novel ADCs have the antigen-antibody binding ability similar to bevacizumab, while also possess strong antitumor activity and vascular normalization activity. In addition, it also showed great tracer ability for transplanted tumors. In summary, the novel ADC showed a surprising vascular normalization-chemotherapy-photodynamic synergistic therapeutic effect, which further enriched the expansion of vascular normalization in the field of new drug discovery.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1079-1087"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801980","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}
Bioconjugate ChemistryPub Date : 2025-05-21Epub Date: 2025-04-11DOI: 10.1021/acs.bioconjchem.4c00584
Célia Sahli, Kenry
{"title":"The Journey and Modes of Action of Therapeutic Nanomaterials in Cells.","authors":"Célia Sahli, Kenry","doi":"10.1021/acs.bioconjchem.4c00584","DOIUrl":"10.1021/acs.bioconjchem.4c00584","url":null,"abstract":"<p><p>Over past decades, a wide range of nanomaterials have been synthesized and exploited to augment the efficacy and biocompatibility of disease theranostics and nanomedicine. The unique physicochemical properties of nanomaterials, such as high specific surface area, tunable size and shape, and versatile surface chemistry, enable the controlled modulation of nanomaterial-biosystem interactions and, consequently, more precise interventions, particularly at the cellular level. The selective modulation of nanomaterial-cell interactions can be leveraged to regulate cellular internalization, intracellular trafficking and localization, and cellular clearance of nanomaterials to enhance the disease therapeutic efficacy and minimize potential cytotoxicity. Herein, we provide an overview of our recent understanding of the journey and modes of action of therapeutic nanomaterials in cells. Specifically, we highlight the various pathways of cellular internalization, trafficking, and excretion of these nanomaterials. The different modes of action of therapeutic nanomaterials, especially controlled release and delivery, photothermal and photodynamic effects, and immunomodulation, are also discussed. We conclude our review by offering some perspectives on the current challenges and potential opportunities in this field.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"914-929"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953155","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}
Bioconjugate ChemistryPub Date : 2025-05-21Epub Date: 2025-05-06DOI: 10.1021/acs.bioconjchem.4c00579
Stanley Sweeney-Lasch, Marie Quillmann, Jens Hannewald, Stephan Dickgiesser, Nicolas Rasche, Min Shan, Carl Deutsch, Stefan Hecht, Jan Anderl, Harald Kolmar, Birgit Piater
{"title":"Elucidating Critical Factors of Internalization and Drug Release of Antibody-Drug Conjugates (ADCs) Using Kinetic Parameters Evaluated by a Novel Tool Named TORCH.","authors":"Stanley Sweeney-Lasch, Marie Quillmann, Jens Hannewald, Stephan Dickgiesser, Nicolas Rasche, Min Shan, Carl Deutsch, Stefan Hecht, Jan Anderl, Harald Kolmar, Birgit Piater","doi":"10.1021/acs.bioconjchem.4c00579","DOIUrl":"10.1021/acs.bioconjchem.4c00579","url":null,"abstract":"<p><p>During the past decade, antibody-drug conjugates (ADCs) have emerged as new drugs in cancer therapy with 15 ADCs already approved such as Kadcyla, Enhertu, and Adcetris. ADCs contain a cytotoxic drug that is linked to an antibody, allowing for specific delivery of the warhead to tumor cells. Typically, the antibody targets a tumor-specific antigen expressed on the cell surface. After the internalization of ADCs into cells, the linker is often cleaved by enzymes in the lysosomal compartment of the cell, releasing the warhead and thereby allowing for its interaction with, for example, the DNA or the tubulin cytoskeleton, which finally leads to cell death. Consequently, binding, internalization, and drug release are key attributes for the efficacy of ADCs. Here, we describe a novel molecule named TORCH (Turn On after Release by CatHepsins) that contains a fluorescence quencher system that is separated by a cathepsin B-cleavable linker. When conjugated to an antibody, the TORCH molecule allows one to gain valuable insights on the internalization and drug release of ADCs. While we cannot exclude the influence of other factors such as receptor recycling, we have found that the receptor density is directly related to the amount of payload released intracellularly, meaning that the internalization per receptor is very similar for all investigated antibodies and cell lines.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"945-959"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952870","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}
Bioconjugate ChemistryPub Date : 2025-05-21DOI: 10.1021/acs.bioconjchem.5c0016310.1021/acs.bioconjchem.5c00163
Yuxiang Cong, Xiaoxing Chen, Thulasiram Bathini, Gang Chen, Da Han, Yangen Huang* and Ruowen Wang*,
{"title":"Design and Synthesis of an Adamantane Phosphoramidite for Programmable and Automated Oligonucleotide-Functionalization","authors":"Yuxiang Cong, Xiaoxing Chen, Thulasiram Bathini, Gang Chen, Da Han, Yangen Huang* and Ruowen Wang*, ","doi":"10.1021/acs.bioconjchem.5c0016310.1021/acs.bioconjchem.5c00163","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00163https://doi.org/10.1021/acs.bioconjchem.5c00163","url":null,"abstract":"<p >Solid-phase synthesis has revolutionized the programmable preparation of oligonucleotides (ONs), enabling precise gene expression modulation and expanding their applications in therapeutic and material sciences. To further enhance ON functionality, this study introduces a novel adamantane-based phosphoramidite for oligonucleotide modification. Adamantane, known for its hydrophobicity and stability, was incorporated into nucleic acid aptamers using automated synthesis. Two aptamers─Sgc8 and AS1411─were functionalized with one or two adamantane units, and the products were purified and validated using high-performance liquid chromatography and mass spectrometry. The incorporation of adamantane significantly altered the aptamers’ polarity and facilitated their self-assembly with poly-β-cyclodextrin, forming stable supramolecular complexes, as demonstrated by polyacrylamide gel electrophoresis. Additionally, adamantane-modified AS1411 exhibited enhanced degradation of its target protein, nucleolin, in MCF-7 cells, suggesting potential utility in targeted protein regulation. These findings establish a versatile platform for functionalizing ONs, broadening their potential for biomedical and nanotechnological applications.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 6","pages":"1311–1318 1311–1318"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305898","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}
Bioconjugate ChemistryPub Date : 2025-05-21DOI: 10.1021/acs.bioconjchem.5c0009810.1021/acs.bioconjchem.5c00098
Raphaël Dutour, and , Gilles Bruylants*,
{"title":"Gold Nanoparticles Coated with Nucleic Acids: An Overview of the Different Bioconjugation Pathways","authors":"Raphaël Dutour, and , Gilles Bruylants*, ","doi":"10.1021/acs.bioconjchem.5c0009810.1021/acs.bioconjchem.5c00098","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00098https://doi.org/10.1021/acs.bioconjchem.5c00098","url":null,"abstract":"<p >Gold-based nanomaterials have marked the last few decades with the emergence of new medical technologies presenting unique features. For instance, the conjugation of gold nanoparticles (AuNPs) and nucleic acids has allowed the creation of nanocarriers with immense promise for gene therapy applications. Although the use of lipid particles as RNA delivery vectors has been broadly explored, this review aims to focus on the limited models reported for the conjugation of RNA with AuNPs. This is nonetheless unexpected regarding the manifold strategies existing to conjugate DNA to gold nanoparticles, which are exhaustively listed in this paper. Furthermore, new processes such as fast microwave and freezing methods have been described very recently, and it therefore seemed necessary to review these recent but promising conjugation pathways and to pick out those applicable to RNA. Indeed, RNA is considerably more attractive than DNA for therapeutic purposes, but its low stability involves numerous difficulties in the construction of effective nanodevices. However, from the many approaches developed for DNA, it turns out that just two of them are frequently used for the building of RNA delivery platforms based on gold: the salt-aging method with thiolated RNA strands and physisorption. However, both approaches present strong limitations such as the low stability of the Au–S bond and the potential cytotoxicity of polycations. To conclude, this general assessment highlights that the exploration of innovating approaches implying different chemistries is needed for the creation of more robust and shapeable AuNPs-RNA conjugates.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 6","pages":"1133–1156 1133–1156"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305884","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}
Zhan Si, Lulu Tian, Hongxin Zhou, Jiasheng Lin and Jun Zhou*,
{"title":"","authors":"Zhan Si, Lulu Tian, Hongxin Zhou, Jiasheng Lin and Jun Zhou*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 5","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.5c00128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144390717","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}