Bioconjugate Chemistry最新文献_第9页

Enhanced Intramuscular mRNA Activity of Peptide–Lipid Nanoparticles with Hydrophobized Head Groups 具有疏水头基团的肽脂纳米颗粒增强肌肉内mRNA活性。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-06-17 Epub Date: 2026-05-25 DOI: 10.1021/acs.bioconjchem.6c00181

Eric Weidinger, Tobias Burghardt, Lennart Obeser, Janin Germer, Jana Pöhmerer, Mina Yazdi, Miriam Höhn, Daniel Merk and Ernst Wagner*,

{"title":"Enhanced Intramuscular mRNA Activity of Peptide–Lipid Nanoparticles with Hydrophobized Head Groups","authors":"Eric Weidinger, Tobias Burghardt, Lennart Obeser, Janin Germer, Jana Pöhmerer, Mina Yazdi, Miriam Höhn, Daniel Merk and Ernst Wagner*, ","doi":"10.1021/acs.bioconjchem.6c00181","DOIUrl":"10.1021/acs.bioconjchem.6c00181","url":null,"abstract":"A library of xenopeptide-based ionizable lipids (XP-ILs) was evaluated in mRNA lipid nanoparticles (LNPs) to investigate the impact of modifications within the polar oligoamine headgroup. Modifications included hydrophobic or bulky side chains or a reduced number of protonatable amines. The resulting XP-ILs were characterized by their key physicochemical properties (logD, logP, HLB, CMC), which were correlated with LNP transfection efficiency and cytotoxicity. The inverse relationship between computational logP and experimental logD5.5 is consistent with the HLB, indicating a lower tendency for water-in-oil micelle formation in carriers with larger hydrophobic headgroups. Four-tailed oleic acid (OleA)4-XP-ILs strongly benefited from a cyclohexyl substituent in the polar ionizable headgroup. Hydrophobization of already highly effective bundle-shaped lipoamino fatty acid (LAF)4-XP-ILs moderately improved efficiency. Notably, intramuscular LNP administration resulted in enhanced in vivo mRNA activity of hydrophobized carriers over previous lead compounds, LAF4-XP (2-fold) and OleA4-XP (12-fold).","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 6","pages":"1257–1269"},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148012501","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

IgG Fc-Binding Motif-Conjugated Exendin-4: A Long-Acting Hypoglycemic Agent via Broad-Spectrum Antibody Engagement for Type 2 Diabetes Therapy IgG fc结合基元偶联扩展蛋白4：通过广谱抗体参与治疗2型糖尿病的长效降糖药。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-06-17 Epub Date: 2026-05-30 DOI: 10.1021/acs.bioconjchem.6c00218

Baojing Mi, Shengjie Ding, Ziyu Tian, Jinhong Yu, Zengxuan Ji, Luwei Fu, Haiyan Liu*, Yuepiao Cai* and Shijie Dai*,

{"title":"IgG Fc-Binding Motif-Conjugated Exendin-4: A Long-Acting Hypoglycemic Agent via Broad-Spectrum Antibody Engagement for Type 2 Diabetes Therapy","authors":"Baojing Mi, Shengjie Ding, Ziyu Tian, Jinhong Yu, Zengxuan Ji, Luwei Fu, Haiyan Liu*, Yuepiao Cai* and Shijie Dai*, ","doi":"10.1021/acs.bioconjchem.6c00218","DOIUrl":"10.1021/acs.bioconjchem.6c00218","url":null,"abstract":"Type 2 diabetes mellitus requires therapies that optimize both efficacy and durability. Although incretin mimetics such as exendin-4 (Ex4) enhance glycemic control, their short half-life restricts their clinical utility. Current extension strategies (e.g., Fc fusion) encounter challenges including immunogenicity and manufacturing complexity. Here, we engineered a series of site-specific IgG Fc-binding motif-modified Ex4 analogues using two orthogonal conjugation methods, leveraging Fc-III-4C-mediated IgG binding (human IgG: KD = 20.1 nM) to achieve a significantly extended plasma half-life. Structure–activity relationship studies revealed that the lead candidate, conjugate 7, retained robust GLP-1R activation and acute glucose-lowering efficacy. In human IgG-preconditioned db/db mice, conjugate 7 achieved a hypoglycemic duration comparable to that of semaglutide. Chronic once-daily dosing of the lead conjugate rivaled semaglutide in reducing HbA1c and protecting pancreatic islets, without toxicity. This strategy leverages >80% of endogenous circulating IgG as a biological reservoir to overcome peptide therapy limitations, offering a translatable platform for long-acting antidiabetic agents.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 6","pages":"1292–1302"},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148100640","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

ssDNA Modification on Lipid Carriers Utilizing ssDNA-Conjugated Fusion Protein with Cholesterol-Binding Ability 利用具有胆固醇结合能力的ssDNA共轭融合蛋白修饰脂质载体。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-06-17 Epub Date: 2026-06-03 DOI: 10.1021/acs.bioconjchem.6c00186

Kei Nishida, Nami Oba, Eiry Kobatake and Masayasu Mie*,

{"title":"ssDNA Modification on Lipid Carriers Utilizing ssDNA-Conjugated Fusion Protein with Cholesterol-Binding Ability","authors":"Kei Nishida, Nami Oba, Eiry Kobatake and Masayasu Mie*, ","doi":"10.1021/acs.bioconjchem.6c00186","DOIUrl":"10.1021/acs.bioconjchem.6c00186","url":null,"abstract":"Lipid carriers, such as liposomes and exosomes, are nanoscale vesicular structures composed of phospholipids, glycolipids, membrane proteins, and cholesterol, which have been widely investigated as drug- and nucleic-acid-delivery systems. Functionalization of lipid carrier surfaces with ligand molecules is an effective approach for the targeted delivery of lipid carriers to specific tissues and cells. In this regard, the use of DNA modification represents a rational and promising approach as DNA aptamers exhibit high affinity and specificity for target molecules and offer several advantages over conventional ligands. The current strategies for modifying lipid carriers with DNA remain suboptimal, leaving room for further improvement. In this study, we aimed to modify lipid carriers with single-stranded (ss)DNA-conjugated fusion proteins that have cholesterol-binding abilities. The fusion protein (Rep-ALOD4) was composed of a replication initiator protein derived from porcine circovirus type 2 (Rep), which acted as an ssDNA-conjugating domain, and domain 4 of anthrolysin O (ALOD4), which acted as a cholesterol-binding domain. As Rep-ALOD4 can bind to cholesterol in lipid membranes under mild conditions, ssDNA-conjugated Rep-ALOD4 achieved ssDNA modification on liposome carriers containing more than 30 wt % cholesterol. Furthermore, cell-selective targeting using DNA aptamer- and ssDNA-modified liposomes and exosomes was successful because of the functional applicability of ssDNA-displaying Rep-ALOD4. Thus, the DNA modification platform of Rep-ALOD4 has the potential to substantially advance targeted drug delivery using lipid carriers.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 6","pages":"1270–1279"},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148147551","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

Enhancing Triggered Release of Polar Cargo from ROS-Responsive Liposomes 增强活性氧响应性脂质体极性货物的触发释放。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-06-17 Epub Date: 2026-06-02 DOI: 10.1021/acs.bioconjchem.6c00158

Annaleena Hansen, Mayesha B. Mustafa, Jinchao Lou and Michael D. Best*,

{"title":"Enhancing Triggered Release of Polar Cargo from ROS-Responsive Liposomes","authors":"Annaleena Hansen, Mayesha B. Mustafa, Jinchao Lou and Michael D. Best*, ","doi":"10.1021/acs.bioconjchem.6c00158","DOIUrl":"10.1021/acs.bioconjchem.6c00158","url":null,"abstract":"Liposomes are promising nanocarriers because of their ability to encapsulate and deliver therapeutic cargo with wide-ranging physicochemical properties. However, liposome delivery could be improved by enhancing triggered release of cargo and particularly doing so in a manner that is selective toward diseased cells. Reactive oxygen species (ROS) provide exciting targets to explore as triggers for the development of stimuli-responsive liposomes due to substantial differences in ROS abundance between diseased versus healthy cells. While our group previously reported ROS-responsive liposomes using a synthetic lipid switch, polar cargo release was slow and limited using our original platform. Herein, we report an improved ROS-responsive lipid switch (2) containing an ROS-responsive boronate ester headgroup attached using an advanced self-immolative linker (SIL) bearing an electron-donating methoxy substituent to a lipid scaffold. Both hydrophobic and hydrophilic fluorescence-based dye release assays showed that liposome formulations including lipid switch 2 were initially stable but successfully released cargo when treated with hydrogen peroxide. Furthermore, dynamic light scattering (DLS) analysis was used to characterize changes in the size and dispersity of liposomes before and after treatment. Ultimately, lipid 2 enabled dramatically faster polar dye cargo release at a lower percentage of incorporation compared to our initial lipid switch. Such improvements increase the prospects of ROS-responsive liposomes for delivery applications.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 6","pages":"1249–1256"},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148141857","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

Noninvasive Characterization of Tumor-Associated Macrophages via [18F]F-Labeled M2-Peptide PET Tracer for Immunotherapy Guidance 用[18F] f标记的m2 -肽PET示踪剂无创表征肿瘤相关巨噬细胞的免疫治疗指导。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-06-17 Epub Date: 2026-05-14 DOI: 10.1021/acs.bioconjchem.6c00183

Xin Lu, Shirui Yang, Jingyi Zhang, Heling Yang, Beilong Zhong*, Guichao Liu* and Duo Xu*,

{"title":"Noninvasive Characterization of Tumor-Associated Macrophages via [18F]F-Labeled M2-Peptide PET Tracer for Immunotherapy Guidance","authors":"Xin Lu, Shirui Yang, Jingyi Zhang, Heling Yang, Beilong Zhong*, Guichao Liu* and Duo Xu*, ","doi":"10.1021/acs.bioconjchem.6c00183","DOIUrl":"10.1021/acs.bioconjchem.6c00183","url":null,"abstract":"M2 macrophages are pivotal in shaping the immunosuppressive microenvironment in the tumor, with their infiltration associated with tumor progression and poor prognosis. However, noninvasive imaging tools for quantitatively assessing tumor M2 macrophages with specificity remain limited. In this study, we developed novel positron emission tomography (PET) tracers based on M2 macrophage-binding peptide (M2pep) to identify optimal one for monitoring tumor immunotherapy. Two M2 macrophage-targeted tracers, [18F]SFB-M2pep and its polyethylene glycol (PEG)-modified [18F]SFB-PEG-M2pep, were designed. The targeting specificity of these tracers was assessed by PET scanning and blocking studies in tumor models. PET imaging demonstrated superior tumor uptake and the ratio of tumor to muscle for [18F]SFB-PEG-M2pep with 1 h postinjection compared to [18F]SFB-M2pep. [18F]SFB-PEG-M2pep was selected for further investigation to assess tumor response to colony-stimulating factor 1 receptor (CSF-1R) blockade. A significant reduction in tracer accumulation in tumors was observed in mice treated with the CSF-1R inhibitor, compared to the control group. This result was confirmed by both immunohistochemistry and flow cytometry. These findings suggest that the novel M2 macrophage-targeted PET tracers, particularly [18F]SFB-PEG-M2pep, have significant potential for precisely monitoring tumor immunotherapy and assessing therapeutic efficacy.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 6","pages":"1280–1291"},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939025","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

Investigating the In Vivo Performance of Tannic Acid-Modified siRNA in the Heart and Liver 单宁酸修饰siRNA在心脏和肝脏中的体内性能研究。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-06-17 Epub Date: 2026-05-27 DOI: 10.1021/acs.bioconjchem.6c00122

O. G. Hayes, J. Rädler, E. Filipiak, T. Czapik, Y. Huang, M. Ojansivu, O. Saher, M. Bood, R. Zain, S. El Andaloussi* and M. Honcharenko*,

{"title":"Investigating the In Vivo Performance of Tannic Acid-Modified siRNA in the Heart and Liver","authors":"O. G. Hayes, J. Rädler, E. Filipiak, T. Czapik, Y. Huang, M. Ojansivu, O. Saher, M. Bood, R. Zain, S. El Andaloussi* and M. Honcharenko*, ","doi":"10.1021/acs.bioconjchem.6c00122","DOIUrl":"10.1021/acs.bioconjchem.6c00122","url":null,"abstract":"Effective extrahepatic activity of therapeutic oligonucleotides remains an unresolved and significant problem in the development of new genetic medicines. Targeted delivery to the heart is of particular interest due to the unmet need to treat an increasing health burden of cardiovascular diseases and the identification of potential genetic therapeutic targets. Drawing inspiration from literature, we investigate the potential of tannic acid (TA) modifications to improve the activity of a model siRNA sequence in the heart. We developed the synthesis of a series of conjugates containing 1–3 (TA) units to study how molecularly defined numbers of TA ligands influence activity. While we observe significant knockdown of the siRNA target gene in the liver, we did not in the heart, suggesting that although TA ligands confer improved function of siRNA in the liver, extrahepatic activity was not enhanced. In addition, hetero-bifunctional siRNA conjugates containing both TA and albumin binding motifs were designed and their synergistic effects explored. Similarly, in vivo data suggests that TA ligands do not increase cardiac activity of siRNA in this context; however, we can conclude that both C16 and AlbuTag ligands do significantly improve siRNA activity in the heart. We believe this work provides important bioconjugation insight for polyphenolic molecules, like tannic acid, as well as the synthesis of hetero-bifunctional siRNA conjugates generally. Moreover, our findings will inform the design of novel targeting ligands and nanomaterials, especially for molecules that may possess emergent properties when present in high multiplicity compared to their monomeric forms.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 6","pages":"1121–1128"},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.6c00122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040075","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}

引用次数: 0

Peptide Tag-nology for Preparation of Site-Specific Antibody–Drug Conjugates 位点特异性抗体-药物偶联物制备的肽标记技术。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-06-17 Epub Date: 2026-05-20 DOI: 10.1021/acs.bioconjchem.6c00154

Alina Ringaci, and , Mark W. Grinstaff*,

引用次数: 0

Homogeneous Antibody–DNA Conjugates Using Unmodified Oligonucleotides and Photo-Cross-Linkable Protein G-HUH Endonuclease Fusion Proteins 使用未修饰的寡核苷酸和光交联蛋白G-HUH内切酶融合蛋白的均质抗体- dna偶联物。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-06-17 Epub Date: 2026-05-13 DOI: 10.1021/acs.bioconjchem.5c00566

Anna Swietlikowska, Femi Hesen, Alexander Gräwe and Maarten Merkx*,

{"title":"Homogeneous Antibody–DNA Conjugates Using Unmodified Oligonucleotides and Photo-Cross-Linkable Protein G-HUH Endonuclease Fusion Proteins","authors":"Anna Swietlikowska, Femi Hesen, Alexander Gräwe and Maarten Merkx*, ","doi":"10.1021/acs.bioconjchem.5c00566","DOIUrl":"10.1021/acs.bioconjchem.5c00566","url":null,"abstract":"Antibody–DNA conjugates are increasingly used in analytical biochemistry and nanotechnology. However, current methods for their preparation often lack specificity, resulting in heterogeneous products. Here, we present a novel strategy to covalently label the Fc domain of antibodies with single-stranded DNA in a site-specific and stoichiometrically controlled manner. This method employs unmodified oligonucleotides and a fusion protein consisting of a protein G dimer linked to an HUH endonuclease. We first evaluated the sequence specificity and optimal conditions for DNA attachment to three HUH endonuclease variants: DCV, PCV2, and WDV. Our results show increased sequence specificity in the presence of Mg2+ compared to the more commonly used Mn2+ cofactor ion. Although formation of the phosphotyrosine bond is found to be reversible, no significant hydrolysis of the protein–DNA conjugates is observed for up to 8 days at room temperature. The DCV domain allowed essentially complete formation of DNA–fusion protein conjugates at a 1:1 protein/DNA ratio, eliminating the need for removal of excess oligos. Subsequent photo-cross-linking yielded antibody–DNA conjugates that were successfully used in a proximity extension assay (PEA) to detect TNFα and IL-6. Our method provides an efficient approach to prepare homogeneous antibody–DNA conjugates with 1:1 stoichiometry.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 6","pages":"1129–1136"},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.5c00566","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147924681","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}

引用次数: 0

Directed Chemical Evolution of Self-Assembling Artificial Proteins Utilizing a Supramolecular System 利用超分子系统的自组装人工蛋白质的定向化学进化。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-06-17 Epub Date: 2026-05-20 DOI: 10.1021/acs.bioconjchem.6c00090

Ashwini R. Khyade, and , Britto S. Sandanaraj*,

{"title":"Directed Chemical Evolution of Self-Assembling Artificial Proteins Utilizing a Supramolecular System","authors":"Ashwini R. Khyade,  and , Britto S. Sandanaraj*, ","doi":"10.1021/acs.bioconjchem.6c00090","DOIUrl":"10.1021/acs.bioconjchem.6c00090","url":null,"abstract":"Nature utilizes nondirected evolution to generate a vast array of biological macromolecules with remarkable diversity and functionality, though at a relatively slow pace. With advances in biotechnology, both directed and nondirected evolution approaches have been employed to design a wide range of biomacromolecules, including self-assembling artificial proteins (SAPs). However, these biological methods are limited to the natural set of 20 amino acids, resulting in SAPs that often lack functional diversity. Chemical approaches, such as micelle-assisted protein labeling technology (MAPLabTech), have enabled the creation of functional SAPs. Despite its potential, MAPLabTech remains a complex, low-throughput, and time-consuming methodology. To overcome these challenges, herein, we disclose a new method, termed Supramolecule-Assisted Protein Labeling Technology (SAPLabTech). In this method, γ-cyclodextrin acts as a host to solubilize hydrophobic chemical probes, forming a cyclodextrin–probe supramolecular complex that enables a site-specific bioconjugation reaction and the synthesis of well-defined monodisperse SAPs in quantitative yield. The versatility of this technology is demonstrated by employing three distinct classes of chemical probes with varying warhead functionalities, linker lengths, and tail hydrophobicity to construct diverse SAP libraries with rich structural features.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 6","pages":"1185–1199"},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147979472","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

The Critical Dosing Interval in Oncology Pretargeted Radionuclide Imaging and Therapy: Mechanisms, Optimization, and Dosimetric Impact 肿瘤预靶向放射性核素成像和治疗的临界剂量间隔：机制、优化和剂量学影响。

IF 4.5 2区化学

Bioconjugate Chemistry Pub Date : 2026-06-17 Epub Date: 2026-05-14 DOI: 10.1021/acs.bioconjchem.6c00042

Yuqi Meng, Huafeng Pang, Wenyao Zhou, Junjie Yan, Chongyang Chen, Donghui Pan, Yuping Xu, Lizhen Wang, Min Yang* and Xinyu Wang*,

{"title":"The Critical Dosing Interval in Oncology Pretargeted Radionuclide Imaging and Therapy: Mechanisms, Optimization, and Dosimetric Impact","authors":"Yuqi Meng, Huafeng Pang, Wenyao Zhou, Junjie Yan, Chongyang Chen, Donghui Pan, Yuping Xu, Lizhen Wang, Min Yang* and Xinyu Wang*, ","doi":"10.1021/acs.bioconjchem.6c00042","DOIUrl":"10.1021/acs.bioconjchem.6c00042","url":null,"abstract":"Pretargeting decouples biologic recognition from radionuclide delivery by administering a primary carrier (P)─such as an antibody, engineered scaffold, nanoparticle, or cell product─bearing capture handles, followed after a delay by a fast-clearing secondary agent (S) retained at target sites through a defined recognition pair (e.g., IEDDA, SPAAC, hybridization, or bsAb–hapten binding). This split-dose architecture suppresses blood-pool background, shortens time-to-readout, and can reduce normal-tissue absorbed dose relative to directly labeled biologics. Across platforms, the P–S dosing interval is the key coordinating variable: it must align (i) high tumor surface-accessible capture-site availability with (ii) sufficiently low circulating P to avoid off-target capture, while matching (iii) S clearance and (iv) radionuclide half-life and workflow constraints. If mistimed, S is consumed in blood and organs, inflating marrow or renal exposure and lowering tumor yield; if optimized, the interval converts biochemical specificity into measurable contrast and therapeutic index. This review focuses on oncology-oriented applications, which currently provide the strongest evidence base for interval optimization in pretargeted radionuclide imaging and therapy. We propose an interval-first design framework: map P blood and tumor kinetics, quantify time-dependent accessible-site dynamics, and perform interval-aware simulations of image quality and dosimetry. We also highlight when clearing or masking agents can expand the actionable window, enabling same-day PET with short-lived nuclides, and propose a minimum reporting checklist to improve reproducibility and cross-study comparison.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 6","pages":"1073–1088"},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147938980","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