Bioconjugate Chemistry最新文献

{"title":"Polysaccharide-Based Coacervate Microgel Bearing Cationic Peptides That Achieve Dynamic Cell-Membrane Structure Alteration and Facile Cytosolic Infusion of IgGs.","authors":"Junya Michibata, Yoshimasa Kawaguchi, Hisaaki Hirose, Akiko Eguchi, Sayaka Deguchi, Kazuo Takayama, Wei Xu, Takuro Niidome, Yoshihiro Sasaki, Kazunari Akiyoshi, Shiroh Futaki","doi":"10.1021/acs.bioconjchem.4c00344","DOIUrl":"10.1021/acs.bioconjchem.4c00344","url":null,"abstract":"<p><p>Conjugates of the biocompatible polysaccharide pullulan with a cell membrane permeabilizing peptide L17E (PL-L17Es) were prepared with the aim of producing complex coacervates with pronounced intracellular antibody (IgG) delivery activity and stable structures. Coacervates with diameters of a few μm were formed simply by mixing PL-L17Es with IgG labeled with negatively charged fluorescent moieties of Alexa Fluor 488 [IgG(AF488)]. The coacervate resulted in a pronounced cytosolic infusion of IgG(AF488) and IgG binding to the target proteins inside the cell. The droplet structures were maintained even under high salt conditions, and the fluorescence in the droplet was not recovered after photobleaching, suggesting the formation of complex coacervate microgels. Dynamic changes in cell membrane structure to entrap the coacervate microgels were captured by confocal and electron microscopy, resulting in cytosolic IgG infusion. The use of M-lycotoxin instead of L17E resulted in a coacervate microgel with marked IgG delivery activity even in the presence of serum. Successful IgG delivery to primary hepatocytes, undifferentiated induced pluripotent stem (iPS) cells, and iPS cell-derived intestinal epithelial cells was also achieved. The construction of complex coacervate microgels with design flexibility and the validity of intracellular IgG delivery with high salt stability were thus demonstrated.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1888-1899"},"PeriodicalIF":4.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581028","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":"Site-Specific Immobilization Boosts the Performance of a Galectin-1 Biosensor.","authors":"Dajana Kolanovic, Rajeev Pasupuleti, Jakob Wallner, Georg Mlynek, Birgit Wiltschi","doi":"10.1021/acs.bioconjchem.4c00467","DOIUrl":"10.1021/acs.bioconjchem.4c00467","url":null,"abstract":"<p><p>The analysis of protein-bound glycans has gained significant attention due to their pivotal roles in physiological and pathological processes like cell-cell recognition, immune response, and disease progression. Routine methods for glycan analysis are challenged by the very similar physicochemical properties of their carbohydrate components. As an alternative, lectins, which are proteins that specifically bind to glycans, have been integrated into biosensors for glycan detection. However, the effectiveness of protein-based biosensors depends heavily on the immobilization of proteins on the sensor surface. To enhance the sensitivity and/or selectivity of lectin biosensors, it is crucial to immobilize the lectin in an optimal orientation for ligand binding without compromising its function. Random immobilization methods often result in arbitrary orientation and reduced sensitivity. To address this, we explored a directed immobilization strategy relying on a reactive noncanonical amino acid (ncAA) and bioorthogonal chemistry. In this study, we site-specifically incorporated the reactive noncanonical lysine derivative, N^ε-((2-azidoethoxy)carbonyl)-l-lysine, into a cysteine-less single-chain variant of human galectin-1 (scCSGal-1). The reactive bioorthogonal azide group allowed the directed immobilization of the lectin on a biosensor surface using strain-promoted azide-alkyne cycloaddition. Biolayer interferometry data demonstrated that the controlled, directed attachment of scCSGal-1 to the biosensor surface enhanced the binding sensitivity to glycosylated von Willebrand factor by about 12-fold compared to random immobilization. These findings emphasize the importance of controlled protein orientation in biosensor design. They also highlight the power of single site-specific genetic encoding of reactive ncAAs and bioorthogonal chemistry to improve the performance of lectin-based diagnostic tools.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1944-1958"},"PeriodicalIF":4.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764560","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":"Renally Excretable Molybdenum Disulfide Nanoparticles as Contrast Agents for Dual-Energy Mammography and Computed Tomography.","authors":"Lenitza M Nieves, Emily K Berkow, Katherine J Mossburg, Nathaniel H O, Kristen C Lau, Derick N Rosario, Priyash Singh, Xingjian Zhong, Andrew D A Maidment, David P Cormode","doi":"10.1021/acs.bioconjchem.4c00508","DOIUrl":"10.1021/acs.bioconjchem.4c00508","url":null,"abstract":"<p><p>Compared with conventional mammography, contrast-enhanced dual-energy mammography (DEM) can improve tumor detection for people with dense breasts. However, currently available iodine-based contrast agents have several drawbacks such as their contraindication for use with renal insufficiency, high-dose requirement, and suboptimal contrast production. Molybdenum disulfide nanoparticles (MoS₂ NPs) have been shown to attenuate X-rays due to molybdenum's relatively high atomic number while having good biocompatibility. However, work exploring their use as X-ray contrast agents has been limited. In this study, we have developed a novel aqueous synthesis yielding ultrasmall, 2 nm MoS₂ NPs with various small molecule coatings, including glutathione (GSH), penicillamine, and 2-mercaptopropionic acid (2MPA). These nanoparticles were shown to have low in vitro cytotoxicity when tested with various cell lines at concentrations up to 1 mg/mL. For the first time, these particles were shown to generate clinically relevant contrast in DEM. In DEM, MoS₂ NPs generated higher contrast than iopamidol, a commercially available X-ray contrast agent, while also generating substantial contrast in CT. Moreover, MoS₂ NPs demonstrated rapid elimination in vivo, mitigating long-term toxicity concerns. Together, the results presented here suggest the potential utility of MoS₂ NPs as a dual-modality X-ray contrast agent for DEM and CT.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"2006-2014"},"PeriodicalIF":4.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764546","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":"Computational Approaches for Antimicrobial Peptide Delivery.","authors":"Thuanny Borba Rios, Samilla Beatriz Rezende, Mariana Rocha Maximiano, Marlon Henrique Cardoso, Martin Malmsten, Cesar de la Fuente-Nunez, Octávio Luiz Franco","doi":"10.1021/acs.bioconjchem.4c00406","DOIUrl":"10.1021/acs.bioconjchem.4c00406","url":null,"abstract":"<p><p>Peptides constitute alternative molecules for the treatment of infections caused by bacteria, viruses, fungi, and protozoa. However, their therapeutic effectiveness is often limited by enzymatic degradation, chemical and physical instability, and toxicity toward healthy human cells. To improve their pharmacokinetic (PK) and pharmacodynamic (PD) profiles, novel routes of administration are being explored. Among these, nanoparticles have shown promise as potential carriers for peptides, although the design of delivery vehicles remains a slow and painstaking process, heavily reliant on trial and error. Recently, computational approaches have been introduced to accelerate the development of effective drug delivery systems for peptides. Here we present an overview of some of these computational strategies and discuss their potential to optimize drug development and delivery.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1873-1882"},"PeriodicalIF":4.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612591","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":"Three Is a Magic Number: Tailored Clickable Chelators Used to Determine Optimal RGD-Peptide Multiplicity in αvβ6-Integrin Targeted ¹⁷⁷Lu-Labeled Cancer Theranostics.","authors":"Tim Rheinfrank, Viktor Lebruška, Stefan Stangl, Margareta Vojtíčková, Nghia Trong Nguyen, Lena Koller, Jakub Šimeček, Vojtěch Kubíček, Susanne Kossatz, Johannes Notni","doi":"10.1021/acs.bioconjchem.4c00481","DOIUrl":"10.1021/acs.bioconjchem.4c00481","url":null,"abstract":"<p><p>The cellular adhesion receptor αvβ6-integrin is highly expressed in many cancers, e.g., pancreatic, lung, head-and-neck, cervical, bladder, and esophageal carcinoma. Multimerization of αvβ6-integrin-specific RGD peptides increases the target affinity and retention but affects biodistribution and pharmacokinetics. Amide formation of the terminal carboxylic acid moieties of the square-symmetrical bifunctional chelator DOTPI with 3-azidopropylamine yields derivatives with 4, 3, and 2 terminal azides and zero, 1, and 2 remaining carboxylic acids, respectively, whereby formation of the 2-cis-isomer is preferred according to NMR investigation of the Eu(III)-complexes. Cu(II)-catalyzed alkyne-azide cycloaddition (CuAAC) of the alkyne-functionalized αvβ6-integrin binding peptide cyclo[YRGDLAYp(<i>N</i>Me)K(pent-4-ynoic amide)] (Tyr2) yields the respective di-, tri-, and tetrameric conjugates for Lu-177-labeling. In mice bearing αvβ6-integrin-expressing xenografts of H2009 (human lung adenocarcinoma) cells, the Lu-177-labeled trimer's tumor-to-blood ratio of 112 exceeds that of the tetramer (10.4) and the dimer (54). Co-infusion of gelofusine (succinylated gelatin) reduces the renal uptake of the trimer by 89%, resulting in a 10-fold better tumor-to-kidney ratio, while no improvement of that ratio is observed with arginine/lysine, <i>para</i>-aminohippuric acid (PAH), and hydroxyethyl starch (HES) coinfusions. Since the Lu-177-labeled Tyr2-trimer outperforms the dimer and the tetramer, such trimers are considered the best lead structures for the ongoing development of αvβ6-integrin targeted anticancer theranostics.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1970-1984"},"PeriodicalIF":4.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749481","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":"Dual Responsive Emulsions Based on Amphiphilic Elastin-like Polypeptide Bioconjugates.","authors":"Laurianne Simon, Dongxu Zhou, Anita Coeurvolan, Vincent Lapinte, Sébastien Lecommandoux, Elisabeth Garanger, Sylvie Bégu","doi":"10.1021/acs.bioconjchem.4c00412","DOIUrl":"10.1021/acs.bioconjchem.4c00412","url":null,"abstract":"<p><p>To achieve the desired therapeutic response, drug delivery systems must ensure the controlled release of the loaded content at the targeted site. One possible strategy relies on the improvement of conventional drug delivery systems. To do so, smart polymers, able to change their behavior upon chemical, physical, or biological stimuli, can be used. In this context, this study aims to evaluate the potential of natural amphiphilic smart elastin-like polypeptides grafted with alkyl chains (ELP-<i>g</i>-Bu) to stabilize conventional oil-in-water emulsions and trigger the release of loaded molecules upon dual stimuli. With butyl pendant chains and methionine residues, the macromolecular surfactant ELP-<i>g</i>-Bu demonstrated a modification of physicochemical properties, looking at critical aggregation concentration, upon both temperature and oxidation stimuli. The macromolecular surfactant was then able to stabilize a paraffin-oil-in-water emulsion. The ELP-<i>g</i>-Bu emulsion presented a droplet size of 9 ± 1 μm and stability for at least a month at 4 and 25 °C. After successful loading of a fluorescent lipophilic molecule used as a drug model, a complete destabilization of the ELP-<i>g</i>-Bu emulsion and burst release of the content was achieved with thermal triggering at 42 °C. In oxidative conditions, a partial release was measured, which can be improved by increasing the number of oxidable thioether groups. Overall, these dually responsive amphiphilic ELP-<i>g</i>-Bu demonstrated their potential for smart-polymer-based drug delivery systems that can be promising for inflammatory disease treatment as increased temperature and radical oxygen species are present in such cases.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1923-1932"},"PeriodicalIF":4.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612592","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":"Gallic Acid-Encapsulated PAMAM Dendrimers as an Antioxidant Delivery System for Controlled Release and Reduced Cytotoxicity against ARPE-19 Cells.","authors":"Aorada Sripunya, Chuda Chittasupho, Supachoke Mangmool, Alexander Angerhofer, Witcha Imaram","doi":"10.1021/acs.bioconjchem.4c00475","DOIUrl":"10.1021/acs.bioconjchem.4c00475","url":null,"abstract":"<p><p>Poly(amidoamine) (PAMAM) dendrimers have gained significant attention in various research fields, particularly in medicinal compound delivery. Their versatility lies in their ability to conjugate with functional molecules on their surfaces and encapsulate small molecules, making them suitable for diverse applications. Gallic acid is a potent antioxidant compound that has garnered considerable interest in recent years. Our research aims to investigate if the gallic acid-encapsulated PAMAM dendrimer generations 4 (G4(OH)-Ga) and 5 (G5(OH)-Ga) could enhance radical scavenging, which could potentially slow down the progression of age-related macular degeneration (AMD). Encapsulation of gallic acid in PAMAM dendrimers is a feasible alternative to prevent its degradation and toxicity. <i>In vitro</i> investigation of antioxidant activity was carried out using the DPPH and ABTS radical scavenging assays, as well as the FRAP assay. The IC₅₀ values for DPPH and ABTS assays were determined through nonlinear dose-response curves, correlating the inhibition percentage with the concentration (μg/mL) of the sample and the concentration (μM) of gallic acid within each sample. G4(OH)-Ga and G5(OH)-Ga possess significant antioxidant activities as determined by the DPPH, ABTS, and FRAP assays. Moreover, gallic acid-encapsulated PAMAM dendrimers inhibit H₂O₂-induced reactive oxygen species (ROS) production in the human retinal pigment epithelium ARPE-19 cells, thereby improving antioxidant characteristics and potentially retarding AMD progression caused by ROS. In an evaluation of cell viability of ARPE-19 cells using the MTT assay, G4(OH)-Ga was found to reduce cytotoxic effects on ARPE-19 cells.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1959-1969"},"PeriodicalIF":4.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783335","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":"Light-Driven Installation of Aminooxyhomolysine on Histones and Its Application for Synthesizing Stable and Site-Specific 3'-DNA-Histone Cross-Links.","authors":"Yangxue Liu, Ying Peng, Zhishuo Wang, Xiaoying Wei, Kun Yang","doi":"10.1021/acs.bioconjchem.4c00453","DOIUrl":"10.1021/acs.bioconjchem.4c00453","url":null,"abstract":"<p><p>Histones react with various aldehyde-containing DNA modifications to form reversible but long-lived DNA-histone cross-links. The investigation of their biochemical effects and repair mechanisms has been impeded due to their reversibility and the lack of methods for synthesizing stable and structure-defined DNA-histone cross-links. Herein, we present a visible-light-driven strategy to install an aminooxyhomolysine on a histone at a defined position. Using this method, we synthesized a hydrolytically stable and site-specific 3'-DNA-histone cross-link derived from an abasic DNA lesion. Such an adduct can be efficiently repaired by proteolysis coupled with nuclease excision. This work provides a strategy that can be readily expanded to synthesize DNA-histone cross-links derived from other aldehyde-containing DNA modifications.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1883-1887"},"PeriodicalIF":4.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638015","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":"Pharmacokinetic Positron Emission Tomography Imaging of an Optimized CD38-Targeted ⁶⁸Ga-Labeled Peptide in Multiple Myeloma: A Pilot Study.","authors":"Qi Yang, Lele Song, Zhao Chen, Yongkang Qiu, Tianyao Wang, Xinyao Sun, Wenpeng Huang, Cuicui Li, Zihua Wang, Lei Kang","doi":"10.1021/acs.bioconjchem.4c00497","DOIUrl":"10.1021/acs.bioconjchem.4c00497","url":null,"abstract":"<p><p>Multiple myeloma (MM) is an incurable disease characterized by its clinical and prognostic heterogeneity. Despite conventional chemotherapy and autologous hematopoietic stem cell transplantation, the management of relapsed and refractory MM disease poses significant challenges, both medically and socioeconomically. CD38, highly expressed on the surface of MM cells, serves as a distinct tumor biological target in MM. Peptides offer advantages over antibodies, enabling precise tumor imaging and facilitating early tumor diagnosis and dynamic immunotherapy monitoring. In this study, we developed PF381, a CD38-targeted peptide, and investigated its role in diagnosis, biodistribution, and dosimetry through ⁶⁸Ga-labeling for preclinical evaluation in tumor-bearing models. We screened a microchip-based combinatorial chemistry peptide library to obtain the amino acid sequence of PF381. Affinity for human CD38 was evaluated by SPRi. PF381 was conjugated with DOTA for radiolabeling with ⁶⁸Ga, and the complex was characterized by HPLC. PET imaging was performed in murine tumor models after the administration of [⁶⁸Ga]Ga-DOTA-PF381. Biodistribution analysis compared CD38-positive H929 and CD38-negative U266 tumors, and human radiation dosimetry was estimated. Tumor sections were stained for CD38 expression. SPRi showed that PF381 had a high affinity for CD38 with a KD of 2.49 × 10^-8 M. HPLC measured a radiolabeling efficiency of 78.45 ± 7.91% for [⁶⁸Ga]Ga-DOTA-PF381, with >98% radiochemical purity. PET imaging revealed rapid and persistent accumulation of radioactivity in CD38-positive H929 tumors, contrasting with negligible uptake in CD38-negative U266 tumors. Biodistribution confirmed higher uptake in H929 tumors (0.75 ± 0.03%ID/g) vs U266 (0.26 ± 0.08%ID/g, <i>P</i> < 0.001). The kidney received the highest radiation dose (3.57 × 10^-02 mSv/MBq), with an effective dose of 1.41 × 10^-02 mSv/MBq. Immunofluorescence imaging supported PET and biodistribution findings. We developed a novel peptide targeting CD38 and proved that ⁶⁸Ga-labeled PF381 had rapid targeting and good tumor penetration capabilities. Therefore, ⁶⁸Ga-labeled PF381 could achieve high sensitivity in vivo imaging for CD38-positive hematological malignancies.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1985-1996"},"PeriodicalIF":4.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612606","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":"^99mTc-Labeled D-Type PTP as a Plectin-Targeting Single-Photon Emission Computed Tomography Probe for Hepatocellular Carcinoma Imaging.","authors":"JiaLi Gong, Meilin Zhu, Lingzhou Zhao, Taisong Wang, Wenli Qiao, Qingqing Huang, Yan Xing, Jinhua Zhao","doi":"10.1021/acs.bioconjchem.4c00492","DOIUrl":"10.1021/acs.bioconjchem.4c00492","url":null,"abstract":"<p><p>Plectin, a scaffolding protein overexpressed in tumor cells, plays a significant role in hepatocellular carcinoma (HCC) proliferation, invasion, and migration. However, the use of L-type peptides for targeting plectin is hindered by their limited stability and retention. We designed a D-type plectin-targeting peptide (^DPTP) and developed a novel single-photon emission computed tomography (SPECT) probe for HCC imaging. The ^DPTP targeting ability was evaluated <i>in vitro</i> using flow cytometry and <i>ex vivo</i> fluorescence imaging. ^99mTc radiolabeling was performed using tricine and ethylenediamine-<i>N</i>,<i>N</i>'-diacetic acid (EDDA) as coligands after modification with 6-hydrazino nicotinamide (HYNIC) at the N termini of ^DPTP. The radiochemical purity (RCP), <i>in vitro</i> stability, and binding affinity of the prepared ^99mTc-HYNIC-^DPTP were analyzed. Tumor uptake, metabolic stability, biodistribution, and pharmacokinetics of ^99mTc-HYNIC-^DPTP were investigated and compared with those of ^99mTc-labeled L-type PTP (^99mTc-HYNIC-PTP) in HCC tumor-bearing mice. ^DPTP could be efficiently radiolabeled with ^99mTc using the HYNIC/tricine/EDDA system with a high RCP and good <i>in vitro</i> stability. Compared with the L-type PTP, ^DPTP exhibited improved targeting ability, and ^99mTc-HYNIC-^DPTP displayed higher tumor uptake, better metabolic stability, longer blood circulation time, and lower kidney retention, resulting in superior imaging performance and biodistribution <i>in vivo</i>. ^99mTc-HYNIC-^DPTP has great potential as a novel SPECT probe for diagnosing HCC.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1997-2005"},"PeriodicalIF":4.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685400","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}