Bioconjugate Chemistry最新文献

Repurposing Lateral Flow Assays as a Versatile and Rapid Characterization Tool for Bioconjugation of Nanoparticles.

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-02-27 DOI: 10.1021/acs.bioconjchem.4c00589

Bryan Gosselin, Raphael Dutour, Julie Janssens, Ivan Jabin, Gilles Bruylants

{"title":"Repurposing Lateral Flow Assays as a Versatile and Rapid Characterization Tool for Bioconjugation of Nanoparticles.","authors":"Bryan Gosselin, Raphael Dutour, Julie Janssens, Ivan Jabin, Gilles Bruylants","doi":"10.1021/acs.bioconjchem.4c00589","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00589","url":null,"abstract":"This study explores the use of lateral flow assays (LFAs), recognized for their simplicity and ease-of-use, as a tool for characterizing nanoparticles functionalized with various biomolecules (e.g., proteins, antibodies, and nucleic acids). A half-strip model system was developed using ovalbumin (OVA) conjugated to gold nanoparticles (AuNPs). The characterization results obtained with LFAs were compared to those from traditional methods such as infrared spectroscopy and fluorescence labeling. The advantages of LFAs in characterizing such conjugated nanosystems were clearly demonstrated. The use of half-strip assays could not only confirm the presence of OVA on AuNPs but also enable the quantification of OVA bound per nanoparticle, offering a rapid and quantitative characterization method. Additionally, the assay showcased its versatility, as it was successfully applied to optimize the covalent coupling conditions of OVA on AuNPs, as well as to differentiate between covalently bound and adsorbed proteins. Furthermore, LFAs were employed to detect antibodies on functionalized nanoparticles, optimize their coupling to a newly developed organic coating, and confirm both the grafting of nucleic acids onto the surface and their pairing with complementary strands. These findings underscore the remarkable adaptability of LFAs for characterizing diverse nanoconjugates. Overall, LFAs stand out as a versatile and accessible tool for characterizing complex bioconjugated nanosystems, making them highly suitable for rapid Quality Control (QC) analysis and bioconjugation optimization.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522200","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

A Near-Infrared Fluorescent Macromolecular Dye for Precise Identification of Glioblastoma Boundaries.

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-02-26 DOI: 10.1021/acs.bioconjchem.5c00019

Jiale Si, Cheng Li, Xin Chen, Qinghao Zhou, Yueming Xue, Yuanyuan Ji, Yansong Dong, Zhishen Ge

{"title":"A Near-Infrared Fluorescent Macromolecular Dye for Precise Identification of Glioblastoma Boundaries.","authors":"Jiale Si, Cheng Li, Xin Chen, Qinghao Zhou, Yueming Xue, Yuanyuan Ji, Yansong Dong, Zhishen Ge","doi":"10.1021/acs.bioconjchem.5c00019","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00019","url":null,"abstract":"Glioblastoma (GBM) is a highly invasive tumor with poorly defined boundaries, often leaving residual tissue after surgery, which contributes to the recurrence and poor prognosis. A critical challenge in GBM treatment is the precise identification of tumor boundaries during surgery to achieve a safe and complete resection. In this study, we present a novel near-infrared fluorescent agent, IR-PEG-cRGD, that is designed to accurately delineate GBM boundaries for surgical navigation of tumor resection. IR-PEG-cRGD is successfully prepared from the cyanine dye IR-820, which is conjugated to poly(ethylene glycol) (PEG) to prolong circulation time and enhance tumor accumulation. Additionally, a glioma-targeting peptide (cRGD, cyclo(Arg-Gly-Asp-d-Phe-Cys)) is conjugated to PEG to selectively target GBM. IR-PEG-cRGD demonstrates effective targeting and enrichment in subcutaneous human-derived GBM mice models, enabling specific distinguishing of the GBM margin from the surrounding parenchyma with a high signal-to-background ratio (SBR) of 4.79. Moreover, IR-PEG-cRGD can pass across the blood-brain barrier (BBB) efficiently. These findings indicate that IR-PEG-cRGD can serve as a valuable tool for the precise intraoperative delineation of GBM boundaries, aiding in safe and complete tumor resection.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497485","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

Transfection via RNA-Based Nanoparticles: Comparing Encapsulation vs Adsorption Approaches of RNA Incorporation.

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-02-25 DOI: 10.1021/acs.bioconjchem.5c00028

Amy E Laturski, Maria T Dulay, Jillian L Perry, Joseph M DeSimone

引用次数: 0

Bioorthogonal Chemical Engineering of rAAV Capsid: Advancing Gene Therapy Targeting Using Proteins.

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-02-24 DOI: 10.1021/acs.bioconjchem.4c00580

Maia Marchand, Sébastien Depienne, Mohammed Bouzelha, Karine Pavageau, Roxane Peumery, Denis Loquet, Dimitri Alvarez-Dorta, Mickaël Guilbaud, Mikaël Croyal, Aurélien Dupont, Oumeya Adjali, Sébastien G Gouin, David Deniaud, Mathieu Mével

{"title":"Bioorthogonal Chemical Engineering of rAAV Capsid: Advancing Gene Therapy Targeting Using Proteins.","authors":"Maia Marchand, Sébastien Depienne, Mohammed Bouzelha, Karine Pavageau, Roxane Peumery, Denis Loquet, Dimitri Alvarez-Dorta, Mickaël Guilbaud, Mikaël Croyal, Aurélien Dupont, Oumeya Adjali, Sébastien G Gouin, David Deniaud, Mathieu Mével","doi":"10.1021/acs.bioconjchem.4c00580","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00580","url":null,"abstract":"We report the chemical conjugation of a recombinant Adeno Associated Virus (rAAV) capsid with various functionalities, including proteins, using a bioorthogonal strategy. rAAVs were azido-coated or dibenzylcyclooctyne (DBCO)-coated by chemically modifying lysine or tyrosine residues. Lysine residues were modified using a phenyl isothiocyanate anchor, and tyrosine residues using either an aryl diazonium salt or a N-methyl luminol derivative. We demonstrate anchor-dependent labeling levels, as observed with biochemical assays and mass spectrometry. Strain-promoted azide-alkyne cycloaddition (SPAAC) was then implemented and evaluated on the rAAV to append functionalities such as fluorescein, biotin, and carbohydrates to the azido-coated capsids. We confirmed the efficiency of the bioorthogonal reaction and observed a stronger reactivity with dibenzylcyclooctyne (DBCO) compared to bicyclononyne (BCN). The optimized SPAAC reaction was finally used to label the viral vectors with two relevant nanobodies targeting specific immune cell receptors (CD62L and CD45). In vitro transduction assays conducted with one rAAV-nanobody conjugate demonstrated the promising targeting properties of these chemically modified vectors. Thus, we anticipate that this strategy will positively impact the field of rAAV capsid engineering and contribute in tissue-specific targeting for the optimization of gene therapy treatments.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490300","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

Gag HIV-1 Virus-like Particles and Extracellular Vesicles Functionalization with Spike Epitopes of SARS-CoV-2 Using a Copper-Free Click Chemistry Approach.

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-02-24 DOI: 10.1021/acs.bioconjchem.4c00559

Marc García-Trujillo, Jesús Lavado-García, Arnau Boix-Besora, Francesc Gòdia, Laura Cervera

{"title":"Gag HIV-1 Virus-like Particles and Extracellular Vesicles Functionalization with Spike Epitopes of SARS-CoV-2 Using a Copper-Free Click Chemistry Approach.","authors":"Marc García-Trujillo, Jesús Lavado-García, Arnau Boix-Besora, Francesc Gòdia, Laura Cervera","doi":"10.1021/acs.bioconjchem.4c00559","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00559","url":null,"abstract":"Enveloped nanoparticles such as extracellular vesicles (EVs) and virus-like particles (VLPs) have emerged as promising nanocarriers capable of transporting bioactive molecules for drug delivery and vaccination. Optimized functionalization methodologies are required to increase the functionalization levels of these nanoparticles, enhancing their performance. Here, a bioorthogonal copper-free strain-promoted azide-alkyne cycloaddition (SPAAC) reaction has been optimized to functionalize human immunodeficiency virus type 1 (HIV-1) Gag-based VLPs and EVs. The optimization process has been carried out through reaction kinetics and design of experiments (DoE) using Cy5 as a reporter molecule. The functionalization of both VLPs and EVs has been studied using super-resolution fluorescence microscopy (SRFM), revealing remarkable differences between Gag-VLPs and coproduced EVs. EVs produced by mock transfection and cell growth have been functionalized achieving a mean of 3618.63 ± 48.91 and 6498.75 ± 352.71 Cy5 molecules covalently linked per particle (Cy5cov/particle), respectively. Different nanoparticles have been functionalized with two linear B-cell epitopes from the Spike protein of SARS-CoV-2, S315-338 TSNFRVQPTESIVRFPNITNLCPF and S648-663 GCLIGAEHVNNSYECD, and analyzed by an immunoassay with sera from COVID-19 patients. The obtained results validate the selected B-cell epitopes and highlight the potential of the optimized functionalization approach for the development of nanoparticle-based vaccines.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490303","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

Lysosome-Specific Delivery of β-Glucosidase Enzyme Using Protein-Glycopolypeptide Conjugate via Protein Engineering and Bioconjugation.

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-02-23 DOI: 10.1021/acs.bioconjchem.4c00430

Abinash Padhy, Mani Gupta, Apurba Das, Isha Farook, Tahiti Dutta, Supratim Datta, Rupak Datta, Sayam Sen Gupta

{"title":"Lysosome-Specific Delivery of β-Glucosidase Enzyme Using Protein-Glycopolypeptide Conjugate via Protein Engineering and Bioconjugation.","authors":"Abinash Padhy, Mani Gupta, Apurba Das, Isha Farook, Tahiti Dutta, Supratim Datta, Rupak Datta, Sayam Sen Gupta","doi":"10.1021/acs.bioconjchem.4c00430","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00430","url":null,"abstract":"Lysosomal enzyme replacement therapy (ERT) holds potential for treating lysosomal storage disorders, but achieving targeted delivery of deficient therapeutic enzymes remains a significant challenge. This study presents a novel approach for the lysosome-specific delivery of the β-glucosidase (B8CYA8) enzyme by covalently conjugating lysosome-targeting mannose-6-phosphate functionalized glycopolypeptides (M6P-GP). We used a protein-glycopolypeptide conjugate developed through advanced protein engineering and bioconjugation techniques. By conjugating β-glucosidase to M6P-GP that has a high affinity for the cation-independent mannose-6-phosphate receptors (CI-MPR) and lysosomal receptors, we enhance the enzyme's selective intracellular uptake and lysosome-specific localization. To attain maximum activity of the near-native enzyme after delivery, we have designed and synthesized an acetal linkage containing the pH-responsive linker maleimide-acetal-azide (MAA), which will cleave in the lysosomal acidic pH to detach the glycopolypeptide from the protein backbone. We demonstrated the efficient cellular uptake of the protein-glycopolypeptide conjugate and showed targeted lysosome delivery, leading to increased enzymatic activity compared to untreated cells. Our results proved that the approach mainly improves the specificity and efficiency of enzyme delivery, particularly into lysosomes, which may enable new methods for ERT. These findings suggest that protein-glycopolypeptide conjugates could represent a class of bioconjugates to design targeted enzyme therapies, offering a pathway to the effective treatment of Gaucher disease (GD) and potentially other related lysosomal storage disorders.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481907","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

T Cell-Targeting Nanotherapies for Atherosclerosis.

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-02-20 DOI: 10.1021/acs.bioconjchem.4c00590

Karla Lambaren, Noah Trac, Daniel Fehrenbach, Meena Madhur, Eun Ji Chung

{"title":"T Cell-Targeting Nanotherapies for Atherosclerosis.","authors":"Karla Lambaren, Noah Trac, Daniel Fehrenbach, Meena Madhur, Eun Ji Chung","doi":"10.1021/acs.bioconjchem.4c00590","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00590","url":null,"abstract":"Cardiovascular diseases remain the leading cause of mortality worldwide. Specifically, atherosclerosis is a primary cause of acute cardiac events. However, current therapies mainly focus on lipid-lowering versus addressing the underlying inflammatory response that leads to its development and progression. Nanoparticle-mediated drug delivery offers a promising approach for targeting and regulating these inflammatory responses. In atherosclerotic lesions, inflammatory cascades result in increased T helper (Th) 1 and Th17 activity and reduced T regulatory activation. The regulation of T cell responses is critical in preventing the inflammatory imbalance in atherosclerosis, making them a key therapeutic target for nanotherapy to achieve precise atherosclerosis treatment. By functionalizing nanoparticles with targeting modalities, therapeutic agents can be delivered specifically to immune cells in atherosclerotic lesions. In this Review, we outline the role of T cells in atherosclerosis, examine current nanotherapeutic strategies for targeting T cells and modulating their differentiation, and provide perspectives for the development of nanoparticles specifically tailored to target T cells for the treatment of atherosclerosis.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466434","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

Chemical Synthesis and Poly(ethylene glycol)-Like Conjugation of the Mango-II Fluorogenic RNA Aptamer.

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-02-20 DOI: 10.1021/acs.bioconjchem.4c00540

Maria Nerantzaki, Claire Husser, Isaure Sergent, Laurence Charles, Jean-François Lutz, Michael Ryckelynck

{"title":"Chemical Synthesis and Poly(ethylene glycol)-Like Conjugation of the Mango-II Fluorogenic RNA Aptamer.","authors":"Maria Nerantzaki, Claire Husser, Isaure Sergent, Laurence Charles, Jean-François Lutz, Michael Ryckelynck","doi":"10.1021/acs.bioconjchem.4c00540","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00540","url":null,"abstract":"A reliable method for the efficient chemical synthesis and poly(ethylene glycol) PEG-like modification of fluorogenic RNA aptamers is reported. The 43-mer version of Mango-II RNA (MangoII-v1), which binds tightly and specifically to the green fluorophore TO1-Biotin (TO1-B), was synthesized by automated phosphoramidite chemistry using 2'-O-[(triisopropylsilyl)oxy]methyl] (2'-O-TOM)-protected ribonucleosides. Solid-phase phosphoramidite chemistry was also used as a single tool to prepare MangoII-v1 modified with a PEG-like oligophosphate synthetic segment (MangoII-v1-P). After cleavage from the resin, deprotection, and purification, the capacity to activate the fluorescence of TO1-B and the degradation behavior of the chemically synthesized RNAs MangoII-v1 and MangoII-v1-P, were deeply investigated in comparison with those of the enzymatically synthesized 48 nucleotides long RNA MangoII. Interestingly, the chemically synthesized MangoII-v1 RNA aptamer demonstrated great activity toward its target, compared to the enzymatically synthesized analogue. Moreover, it was found to be highly stable, retaining its structural integrity and bioactivity, even after seven days of incubation in 20% fetal bovine serum. MangoII-v1-P also showed a high affinity for TO1-B and excellent degradation resistance.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466422","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

Conditional Control of Benzylguanine Reaction with the Self-Labeling SNAP-tag Protein.

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-02-20 DOI: 10.1021/acs.bioconjchem.5c00002

Steven E Caldwell, Isabella R Demyan, Gianna N Falcone, Avani Parikh, Jason Lohmueller, Alexander Deiters

{"title":"Conditional Control of Benzylguanine Reaction with the Self-Labeling SNAP-tag Protein.","authors":"Steven E Caldwell, Isabella R Demyan, Gianna N Falcone, Avani Parikh, Jason Lohmueller, Alexander Deiters","doi":"10.1021/acs.bioconjchem.5c00002","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00002","url":null,"abstract":"SNAP-tag, a mutant of the O6-alkylguanine-DNA-alkyltransferase, self-labels by reacting with benzylguanine (BG) substrates, thereby forming a thioether bond. SNAP-tag has been genetically fused to a wide range of proteins of interest in order to covalently modify them. In the context of both diagnostic and therapeutic applications, as well as use as a biological recording device, precise control in a spatial and temporal fashion over the covalent bond-forming reaction is desired to direct inputs, readouts, or therapeutic actions to specific locations, at specific time points, in cells and organisms. Here, we introduce a comprehensive suite of six caged BG molecules: one light-triggered and five others that can be activated through various chemical and biochemical stimuli, such as small molecules, transition metal catalysts, reactive oxygen species, and enzymes. These molecules are unable to react with SNAP-tag until the trigger is present, which leads to near complete SNAP-tag conjugation, as illustrated both in biochemical assays and on human cell surfaces. This approach holds promise for targeted therapeutic assembly at disease sites, offering the potential to reduce off-target effects and toxicity through precise trigger titration.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466431","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

[¹⁷⁷Lu]Lu-XYIMSR-01: A Novel CAIX-Targeted Radiotherapeutic for Enhanced Treatment of Malignant Glioma.

IF 4 2区化学

Bioconjugate Chemistry Pub Date : 2025-02-20 DOI: 10.1021/acs.bioconjchem.5c00041

Jing Wang, Chengxue He, Rui Guo, Li Wen, Jinping Tao, Huimao Zhang, HaiFeng Huang, Hua Zhu, Zhi Yang, Xianteng Yang

{"title":"[177Lu]Lu-XYIMSR-01: A Novel CAIX-Targeted Radiotherapeutic for Enhanced Treatment of Malignant Glioma.","authors":"Jing Wang, Chengxue He, Rui Guo, Li Wen, Jinping Tao, Huimao Zhang, HaiFeng Huang, Hua Zhu, Zhi Yang, Xianteng Yang","doi":"10.1021/acs.bioconjchem.5c00041","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00041","url":null,"abstract":"Malignant glioma highly expresses carbonic anhydrase IX (CAIX). This study aimed to develop [177Lu]Lu-XYIMSR-01, a small-molecule therapeutic agent CAIX, to assess its potential for treating malignant glioma. [177Lu]Lu-XYIMSR-01 was synthesized by radiolabeling DOTA-XYIMSR-01 with 177Lu. In vitro assays were conducted to evaluate the affinity for U87MG tumor cells. The probe was injected via the tail vein into subcutaneous and orthotopic U87MG models for micro-SPECT/CT imaging. The survival rates of tumor-bearing mice were assessed after [177Lu]Lu-XYIMSR-01 injection by intratumoral in orthotopic models, including untreated controls and those treated with Temozolomide or combination therapy. After purification, the radiochemical yield of [177Lu]Lu-XYIMSR-01 was 86.47 ± 2.42%, with a radiochemical purity (RCP) of 99%. Its cell uptake in U87MG cells was 3.70 ± 0.57 ‰ AD/105 cells, significantly higher than that in HCT116 cells (0.68 ± 0.16 ‰ AD/105 cells, P = 0.001). In the biodistribution study, [177Lu]Lu-XYIMSR-01 uptake in U87MG tumors was 6.19 ± 1.37%ID/g, with a tumor/muscle ratio of 20.14 ± 3.24. In the orthotopic glioma model, local injection combined with Temozolomide significantly improved survival and inhibited tumor growth. The results indicate that [177Lu]Lu-XYIMSR-01 is a promising therapeutic molecular probe for targeting CAIX, and its combination with Temozolomide significantly enhances treatment outcomes for malignant glioma.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466677","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