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,&nbsp;Merin K. Abraham,&nbsp;Geneva Indongo,&nbsp;Greeshma Rajeevan,&nbsp;Arathy B. K. Kala,&nbsp;Aishwarya Lekshman and Sony George*,&nbsp;","doi":"10.1021/acs.bioconjchem.5c0019110.1021/acs.bioconjchem.5c00191","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00191https://doi.org/10.1021/acs.bioconjchem.5c00191","url":null,"abstract":"<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":"36 6","pages":"1329–1339 1329–1339"},"PeriodicalIF":4.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306025","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":"Genetic Engineering of VHH Antibody Fragments for Efficient Site-Specific Conjugation to Polysaccharides","authors":"Lin Zhong,&nbsp;Lisanne C. M. Morshuis,&nbsp;Michelle Koerselman,&nbsp;Angela Memelink,&nbsp;Anna Kolecka,&nbsp;Raimond Heukers,&nbsp;Theo Verrips,&nbsp;Marcel Karperien* and Bram Zoetebier*,&nbsp;","doi":"10.1021/acs.bioconjchem.5c0016710.1021/acs.bioconjchem.5c00167","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00167https://doi.org/10.1021/acs.bioconjchem.5c00167","url":null,"abstract":"<p >Site-selective modifications of proteins, without compromising their biological activity, are highly sought after due to their critical role in many biomedical applications. Here, we established a universal and efficient approach for site-selective conjugation of a variable domain of single-chain heavy-chain only antibody fragments (VHH) to polysaccharides using thiol–maleimide chemistry, known for its specificity and efficiency. This is achieved by genetically engineering an unpaired cysteine (Cys) residue in a C-terminal extension of VHHs. In this study, we synthesized two maleimide-functionalized polysaccharides, i.e., dextran-maleimide (Dex-Mal) and hyaluronic acid-maleimide (HA-Mal), for protein conjugation. Six distinct VHHs were selected and engineered with C-terminal extensions containing Cys residues for conjugation with Dex-Mal and HA-Mal. Conjugation efficiency varied among VHHs due to structural heterogeneity, which influenced the reactivity of the engineered Cys residues. One VHH, specific to TNFα (anti-TNFα-VHH), exhibited low conjugation efficiency (&lt;20%); however, efficiency was fully restored when a flexible glycine-serine G₄S linker was introduced between the variable domain and the C-terminal Cys tag. Additionally, incorporation of two free Cys residues in the C-terminal tail further enhanced conjugation efficiency. This work establishes a robust and versatile approach for generating protein–polysaccharide conjugates, paving the way for therapeutic and diagnostic applications.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 6","pages":"1319–1328 1319–1328"},"PeriodicalIF":4.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.bioconjchem.5c00167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305913","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":"Targeting HER2 with DNA Aptamers for Efficient Anticancer Drug Delivery: A Combined Experimental and Computational Study","authors":"Konstantin E. Katsuba,&nbsp;Lidia M. Zabegina,&nbsp;Daniil S. Plevako,&nbsp;Andrey A. Gurtovenko and Anastasia V. Malek*,&nbsp;","doi":"10.1021/acs.bioconjchem.5c0002210.1021/acs.bioconjchem.5c00022","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00022https://doi.org/10.1021/acs.bioconjchem.5c00022","url":null,"abstract":"<p >Targeted delivery of cytostatic drugs is a powerful approach to achieving tumor tissue selectivity, reducing systemic toxicity, and ultimately improving the efficacy of anticancer chemotherapy. Targeting can be achieved using a wide range of molecular ligands, with DNA aptamers being a promising representative. In this work, we employed flow cytometry, a AuNP-aptasensor, and atomic-scale computer modeling to assess the affinity of several DNA aptamers (Anti-HER2, HB5, Apt-6, HeA2_1, and HeA2_3) for human epidermal growth factor receptor 2 (HER2), which is known to be one of the factors that promote the growth of breast cancer cells. Flow cytometry showed that short aptamers (HeA2_1 and HeA2_3) had a higher affinity for HER2 on MDAMB453 cancer cells than longer aptamers (HB5, Apt-6). HER2-negative MDA-MB-231 cells served as the negative control. The HeA2_3 aptamer has a high average affinity (HeA2_3:23.6, HeA2_1:13.1, Apt-6:3.6; HB5:3.5; Anti-HER2:3.2) and a nearly Gaussian distribution across the cells, while HeA2_1 forms a fraction of cells with a relatively high fluorescence signal intensity (HeA2_1:11.6; HeA2_3:5.9; Apt-6:3.4; HB5:3.1; Anti-HER2:2.1). Most of the findings for cancer cells also hold for the HER2-positive small extracellular vesicles studied using the AuNP-aptasensor. Computer simulations confirmed that short aptamers are characterized by stronger binding to the extracellular domain of HER2. A detailed analysis of the free energy allowed us to show for the first time that tight binding to HER2 correlates with well-separated hot and cold spots on the protein surface. For the aptamers that meet these criteria (HeA2_1, HeA2_3, and Anti-HER2), favorable interactions with HER2 are driven by the local attraction of nucleotides to arginine and lysine residues of HER2 and possibly stabilized by intermolecular hydrogen bonds. For longer aptamers (Apt-6 and HB5), hot and cold spots on the HER2 surface overlap and the aptamers show much weaker binding. Overall, our findings show that binding of DNA aptamers to HER2 cannot be characterized merely by the dissociation equilibrium constant. A more sophisticated approach that combines experimental and computational methods allowed us to unlock the molecular mechanisms behind the aptamer–HER2 bindings. The results of our study also suggest that computer modeling has become a reliable and accurate tool for aptamer prescreening prior to laboratory experiments.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 6","pages":"1180–1196 1180–1196"},"PeriodicalIF":4.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305901","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":"Facially Amphiphilic Cholate-Conjugated Polymers for Regulating Insulin Fibrillation.","authors":"Desoshree Ghosh, Sagar Bag, Priyadarsi De","doi":"10.1021/acs.bioconjchem.5c00097","DOIUrl":"10.1021/acs.bioconjchem.5c00097","url":null,"abstract":"<p><p>To understand the influence of facially amphiphilic polymers (FAPs) on insulin fibril (IF) inhibition, three different cholate-based FAPs [cationic (<b>PFCAQA</b>), anionic (<b>PFCASF</b>), and zwitterionic (<b>PFCASB</b>)] have been synthesized. Besides, two control polymers [cholate and sulfobetaine-pendant random copolymer <b>PRCASB</b> (without facial amphiphilicity) and sulfobetaine-tethered homopolymer <b>PSBMA</b> (without cholate pendants)] are also prepared. Several biophysical experiments such as spectroscopic techniques [thioflavin T (ThT), Nile red (NR), tyrosine (Tyr) fluorescence assay], turbidity assay by ultraviolet-visible (UV-vis) spectroscopy, dynamic light scattering (DLS), circular dichroism (CD) study, and microscopic investigation are performed to investigate the role of polymers as antiamyloidogenic agents during insulin fibrillation. Interestingly, the <b>PFCASB</b> zwitterionic polymer behaves as the most efficacious antiamyloidogenic agent. To clarify the interaction of <b>PFCASB</b> and native insulin (NI), an isothermal titration calorimetry (ITC) experiment is carried out. Tyr and the NR fluorescence investigation suggest the important role of hydrophobic interactions, whereas the ITC experiment confirms the significance of hydrophobic and electrostatic interactions in the IF inhibitory process. A hemolytic test is conducted to investigate the toxicity caused by IF and the efficacy of <b>PFCASB</b> in prohibiting erythrocyte disruption caused by IF. Overall, the present work reveals the impact of the facially amphiphilic cholic acid (CA)-based zwitterionic polymer in modulating the insulin aggregation process and gives a new perspective for investigations on different protein aggregations.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1040-1053"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952257","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":"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 NH₂-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^-2 to 10³ 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}

{"title":"","authors":"Yun Feng,&nbsp;Zifan Zhu,&nbsp;Shirui Zhao,&nbsp;Xingyu Jiang,&nbsp;Wen Zhang and Zhiai Xu*,&nbsp;","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.5c00109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144390709","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":"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}

{"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}

{"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}

{"title":"","authors":"Yong-Shan Zheng,&nbsp;Teng Zhang,&nbsp;Ji-Yang Song,&nbsp;Mingchan Liang,&nbsp;Ya-Li Liu,&nbsp;Zeng-Guang Xu,&nbsp;Cheng He* and Zhan-Yun Guo*,&nbsp;","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.5c00026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144360956","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}