Bioconjugate Chemistry最新文献

{"title":"Targeted Delivery of TLR7 Agonists to the Tumor Microenvironment Enhances Tumor Immunity via Activation of Tumor-Resident Myeloid Cells.","authors":"Emanuela Sega, Srikanth Kotapati, Yam B Poudel, Qinqin Cheng, Keerthi Sadanala, Bridget Schneider, Eugene P Chekler, Chetana Rao, Sanjeev Gangwar, Tim Sproul, Deborah Law, Miranda Broz, Pavel Strop, Sayumi Yamazoe","doi":"10.1021/acs.bioconjchem.4c00534","DOIUrl":"10.1021/acs.bioconjchem.4c00534","url":null,"abstract":"<p><p>Toll-like receptors (TLR) are phylogenetically conserved mediators of innate immunity that are essential for establishing adaptive immune responses against invading pathogens. TLR7 is an endosomal receptor expressed predominantly in myeloid and B cells. Activation of TLR7 induces Type I interferon and proinflammatory responses; therefore, targeting TLR7 is a promising strategy for antitumor therapy. Although the use of bacterial components to trigger innate immune responses in cancer patients started a century ago, the effectiveness of systemic TLR agonists has been rather underwhelming in clinical trials, partly due to nonspecific immune activation leading to safety and tolerability issues. Antibody-drug conjugates (ADCs) constitute a proven therapeutic modality amenable to systemic administration with limited toxicity concerns via a targeted delivery platform. We generated TLR7 agonist-antibody conjugates that recognize tumor antigens expressed on the surface of tumor cells. Generated ADCs demonstrated robust activity in in vitro tumor antigen-presenting cell (APC) coculture systems as indicated by dose-dependent upregulation of PD-L1 and CD86 on macrophages. TLR7 agonist-ADC provided superior tumor growth control compared to intravenously (IV) administrated free TLR7 agonist. Treatment with TLR7 agonist-ADC led to prolonged activation of myeloid cells in the tumor microenvironment (TME) with minimum immune activation in the periphery. Systemic and tissue exposure studies demonstrated tumor-specific free drug release by targeted ADC treatment. In summary, the TLR7 agonist-ADC can potentially activate immune cells in the TME to generate tumor antigen-specific T-cell responses, making it an attractive approach for precision cancer therapy.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"437-448"},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412270","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":"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":"10.1021/acs.bioconjchem.5c00002","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"540-548"},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926790/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Lipidation on the Structure, Oligomerization, and Aggregation of Glucagon-like Peptide 1.","authors":"Eva Přáda Brichtová, Irina A Edu, Xinyang Li, Frederik Becher, Ana L Gomes Dos Santos, Sophie E Jackson","doi":"10.1021/acs.bioconjchem.4c00484","DOIUrl":"10.1021/acs.bioconjchem.4c00484","url":null,"abstract":"<p><p>Lipidated analogues of glucagon-like peptide 1 (GLP-1) have gained enormous attention as long-acting peptide therapeutics for type 2 diabetes and also antiobesity treatment. Commercially available therapeutic lipidated GLP-1 analogues, semaglutide and liraglutide, have the great advantage of prolonged half-lives <i>in vivo</i> of hours and days instead of minutes as is the case for native GLP-1. A crucial factor in the development of novel lipidated therapeutic peptides is their physical stability, which greatly influences manufacturing and drug product development. This work provides a systematic study of the solubility, structure, oligomerization, and long-term stability of five different lipidated analogues of GLP-1, varying in the position of the lipidation site and the nature of lipid attachment. The lipidation was found to negatively impact the peptide solubility, in all cases, limiting it to a specific pH range. An increase in the α-helical secondary structure was observed upon lipidation, and the lipidated analogues were found to form larger and more stable oligomeric species compared to nonlipidated GLP-1. Importantly, the distributions and populations of oligomeric species formed were regulated by both the position and the nature of the lipidation. During the 6 days of sample aging, several lipidated analogues formed aggregates with variable morphologies ranging from elongated mature fibrils to amorphous structures. The kinetics of aggregation often showed multiple steps and did not follow a standard nucleation-propagation mechanism. A wide range of behaviors was observed, and while our observations indicate that the formation of a single stable oligomer results in the greatest physical stability, positioning the lipid group toward the N-terminus of the peptide results in extremely rapid amyloid formation. We believe that our study provides important findings for the development of long-acting lipidated analogues of peptide therapeutics.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"401-414"},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996179","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":"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":"10.1021/acs.bioconjchem.4c00540","url":null,"abstract":"<p><p>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'-<i>O</i>-[(triisopropylsilyl)oxy]methyl] (2'-<i>O</i>-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-<b>P</b>). 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-<b>P</b>, 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-<b>P</b> also showed a high affinity for TO1-B and excellent degradation resistance.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"449-456"},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","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}

{"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":"10.1021/acs.bioconjchem.5c00041","url":null,"abstract":"<p><p>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, <i>P</i> = 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.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"588-596"},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","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}

{"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":"10.1021/acs.bioconjchem.4c00559","url":null,"abstract":"<p><p>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 (Cy5_cov/particle), respectively. Different nanoparticles have been functionalized with two linear B-cell epitopes from the Spike protein of SARS-CoV-2, S_315-338 TSNFRVQPTESIVRFPNITNLCPF and S_648-663 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.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"486-499"},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","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}

{"title":"FeOOH-Assisted Formation of Hybrid Polymer Nanospindles for Efficient Iron Delivery and Ferroptosis Tumor Therapy.","authors":"Heng Liu, Lu Wang, Hao Jin, Kepeng Tao, Xuanqi Zhu, Mengsi Zhang, Yuchuan Hou, Shuwei Liu, Hao Zhang","doi":"10.1021/acs.bioconjchem.4c00546","DOIUrl":"10.1021/acs.bioconjchem.4c00546","url":null,"abstract":"<p><p>Exogenous iron delivery using iron-containing nanomaterials is an alternative strategy for enhancing the efficacy in ferroptosis tumor therapy but limited by the problems of low iron content, low tumor enrichment, low cellular uptake, and uncontrolled release of iron ions. To solve the problems, an FeOOH-assisted approach is demonstrated to produce iron hybrid polymer nanospindles (IHPNSs) for efficient iron delivery and ferroptosis tumor therapy. The IHPNSs are prepared through the cohydrolysis of FeCl₃·6H₂O with aniline, pyrrole, or amino-pyrrole. On the one hand, the hydrolysis of Fe³⁺ generates FeOOH particles, which further act as the templates to form fusiform architectures. On the other hand, Fe³⁺ triggers the oxidative polymerization of aniline, pyrrole, or amino-pyrrole. The as-prepared polymers are capable of coordinating with excessive Fe³⁺ and locate on the FeOOH templates, thus producing Fe³⁺/polymer composite-coated FeOOH nanospindles. Systematic studies indicate that the one-dimension-like morphology facilitates tumor enrichment and cellular uptake of IHPNSs. Besides the high iron content of IHPNSs, the controlled release of Fe³⁺ stimulated by the overexpressed glutathione (GSH) in the tumor microenvironment is achieved. The released Fe³⁺ is further transformed to Fe²⁺ by scavenging GSH, which leads to excessive accumulation of reactive oxygen species and lipid peroxides and finally induces ferroptosis of tumor cells. As a proof of concept, the IHPNSs show good efficacy in the treatment of a rat model of bladder tumors in situ.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"464-475"},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565615","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":"Improved Pendant-Bearing Glucose-Neopentyl Glycols for Membrane Protein Stability.","authors":"Taeyeol Youn, Ganghee Kim, Parameswaran Hariharan, Xianglan Li, Waqar Ahmed, Bernadette Byrne, Xiangyu Liu, Lan Guan, Pil Seok Chae","doi":"10.1021/acs.bioconjchem.4c00556","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.4c00556","url":null,"abstract":"<p><p>Membrane proteins are biologically and pharmaceutically significant, and determining their 3D structures requires a membrane-mimetic system to maintain protein stability. Detergent micelles are widely used as membrane mimetics; however, their dynamic structures often lead to the denaturation and aggregation of encapsulated membrane proteins. To address the limitations of classical detergents in stabilizing membrane proteins, we previously reported a class of glucose-neopentyl glycols (GNGs) and their pendant-bearing versions (P-GNGs), several of which proved more effective than DDM in stabilizing membrane proteins. In this study, we synthesized additional GNG derivatives by varying the lengths of the pendant (P-GNGs), and by introducing hemifluorinated pendants to the GNG scaffold (fluorinated pendant-bearing GNGs or FP-GNGs). The synthetic flexibility of the GNG chemical architecture allowed us to create a diverse range of derivatives, essential for the effective optimization of detergent properties. When tested with two model membrane proteins (a transporter and a G-protein coupled receptor (GPCR)), most of the new (F)P-GNGs demonstrated superior stabilization of these membrane proteins compared to DDM, the original GNG (OGNG)), and a previously developed P-GNG (i.e., GNG-3,14). Notably, several P-GNGs synthesized in this study were as effective as or even better than lauryl maltose neopentyl glycol (LMNG) in stabilizing a human GPCR, beta2 adrenergic receptor (β2AR). Enhanced protein stability was particularly observed for the P-GNGs with a butyl (C4) or pentyl (C5) pendant, indicating that these pendant sizes are optimal for membrane protein stability. The volumes of these pendants appear to minimize the empty spaces in the micelle interiors, thereby enhancing detergent-detergent interactions in micelles complexed with the membrane proteins. Additionally, we identified one FP-GNG that was more efficient at extracting the transporter and more effective at stabilizing the GPCR than DDM. Thus, the current study demonstrates that both chain length and number of fluorine atoms in the pendants of the P-GNGs were crucial determinants for membrane protein stability. We not only developed a few (F)P-GNGs that are significantly more effective than maltoside detergents (LMNG/DDM) for protein extraction and stability but we also provided an effective strategy for detergent design through the utilization of partially fluorinated pendants of varying length.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655463","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":"Transfection via RNA-Based Nanoparticles: Comparing Encapsulation vs Adsorption Approaches of RNA Incorporation.","authors":"Amy E Laturski, Maria T Dulay, Jillian L Perry, Joseph M DeSimone","doi":"10.1021/acs.bioconjchem.5c00028","DOIUrl":"10.1021/acs.bioconjchem.5c00028","url":null,"abstract":"<p><p>Historically, RNA delivery via nanoparticles has primarily relied on encapsulation, as demonstrated by lipid nanoparticles in SARS-CoV-2 vaccines. Concerns about RNA degradation on nanoparticle surfaces initially limited the exploration of adsorption-based approaches. However, recent advancements have renewed interest in adsorption as a viable alternative. This Viewpoint explores the approaches of RNA incorporation in nanoparticles, comparing encapsulation, adsorption, and the combination of encapsulation and adsorption, and presents a framework to guide the selection of the most suitable strategy based on general characteristics.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"367-376"},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497498","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":"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":"10.1021/acs.bioconjchem.5c00019","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"578-587"},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","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}