Bioconjugate Chemistry最新文献

Functional Bioimaging Probes: Fluorescent Conjugated Polymer Nanoparticles Coupled with Pleural Fluid-Derived Peptides and Proteins. 功能性生物成像探针：荧光共轭聚合物纳米颗粒与胸膜液衍生肽和蛋白质耦合。

IF 3.9 2区化学

Bioconjugate Chemistry Pub Date : 2025-09-12 DOI: 10.1021/acs.bioconjchem.5c00321

Kerem Tok, Hichem Moulahoum, F Baris Barlas, Oguzhan Karakurt, Nursima Ucar, Didem Aksu, Dilara Yeniterzi, Ozge Ozufuklar, Dilara Gürsoy, Saniye Soylemez, Emine Guler Celik, Ali Cirpan, Tevfik Ilker Akcam, Kutsal Turhan, Figen Zihnioglu, Suna Timur

{"title":"Functional Bioimaging Probes: Fluorescent Conjugated Polymer Nanoparticles Coupled with Pleural Fluid-Derived Peptides and Proteins.","authors":"Kerem Tok, Hichem Moulahoum, F Baris Barlas, Oguzhan Karakurt, Nursima Ucar, Didem Aksu, Dilara Yeniterzi, Ozge Ozufuklar, Dilara Gürsoy, Saniye Soylemez, Emine Guler Celik, Ali Cirpan, Tevfik Ilker Akcam, Kutsal Turhan, Figen Zihnioglu, Suna Timur","doi":"10.1021/acs.bioconjchem.5c00321","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00321","url":null,"abstract":"Thiol-functionalized conjugated polymers offer a versatile platform for designing fluorescent nanomaterials with biomedical relevance. In this study, a thiol modified conjugated polymer composed of benzoxadiazole (BO) and carbazole (POxC-SH) was synthesized, then converted into fluorescent nanoparticles (POxC-SH NPs) via a reprecipitation method. The nanoparticles exhibited strong photoluminescence, colloidal stability, and monodispersity in media. Surface thiol groups enabled conjugation with peptide and protein components isolated from the pleural fluid of lung adenocarcinoma patients using SMCC cross-linking. The resulting bioconjugated nanoprobe was characterized by spectroscopic methods, FTIR, XPS, and Mass spectrometry. Cellular studies in A549 and BEAS-2B cell lines demonstrated efficient internalization and low toxicity of both native and conjugated nanoparticles. This work presents a proof of concept for using thiol-modified conjugated polymer nanoparticles as intrinsically fluorescent, patient-adaptable imaging agents, bridging conjugated polymer chemistry with targeted biomedical applications.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051344","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

Dopamine Carbon Dots Synergize with Mild Photothermal Therapy for Anti-Inflammatory Treatment of Periodontitis. 多巴胺碳点与轻度光热疗法协同抗炎治疗牙周炎。

IF 3.9 2区化学

Bioconjugate Chemistry Pub Date : 2025-09-12 DOI: 10.1021/acs.bioconjchem.5c00327

Ting Zhao, Meijing Mu, Haoyu Yin, Yang Yang, Wenhuan Bu, Hongchen Sun

{"title":"Dopamine Carbon Dots Synergize with Mild Photothermal Therapy for Anti-Inflammatory Treatment of Periodontitis.","authors":"Ting Zhao, Meijing Mu, Haoyu Yin, Yang Yang, Wenhuan Bu, Hongchen Sun","doi":"10.1021/acs.bioconjchem.5c00327","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00327","url":null,"abstract":"Periodontitis is a chronic inflammatory oral disease characterized by dysregulated host immune responses. Modulating the immune microenvironment has emerged as a promising therapeutic strategy to address the limitations of conventional treatments. To explore this approach, we developed uniformly sized dopamine-derived carbon dots (DACDs) with smooth surfaces via hydrothermal synthesis using dopamine as the precursor. The synthesized DACDs exhibited favorable biosafety and considerable photothermal conversion capability. In vitro experiments employing quantitative real-time PCR (qRT-PCR), Western blotting, and immunofluorescence staining demonstrated that DACDs synergized with mild photothermal therapy (MPTT) to significantly downregulate pro-inflammatory cytokine expression in RAW264.7 cells. In vivo studies further confirmed that the combined application of DACDs and MPTT markedly reduced periodontal inflammation and attenuated alveolar bone resorption, as evidenced by Micro-CT analysis and histological staining. Collectively, DACDs mitigate bone destruction by suppressing inflammatory cascades, establishing a novel and effective immunomodulatory strategy for the management of periodontitis.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051330","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 Next-Generation Brain-Targeting Peptide: KS-487 Rivals Angiopep-2 in BBB Penetration with Enhanced Selectivity. 新一代脑靶向肽：KS-487与Angiopep-2在血脑屏障穿透中的选择性增强

IF 3.9 2区化学

Bioconjugate Chemistry Pub Date : 2025-09-11 DOI: 10.1021/acs.bioconjchem.5c00352

Kensuke Asukabe, Nagi Yamashita, Runa Fujimoto, Kotaro Sakamoto, Eijiro Miyako

{"title":"A Next-Generation Brain-Targeting Peptide: KS-487 Rivals Angiopep-2 in BBB Penetration with Enhanced Selectivity.","authors":"Kensuke Asukabe, Nagi Yamashita, Runa Fujimoto, Kotaro Sakamoto, Eijiro Miyako","doi":"10.1021/acs.bioconjchem.5c00352","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00352","url":null,"abstract":"KS-487 is a cyclic peptide previously reported to bind low-density lipoprotein receptor-related protein 1 (LRP1) and exhibit blood-brain barrier (BBB) permeability. In this study, we evaluated the in vivo BBB permeability and selectivity of KS-487 in comparison with those of Angiopep-2 (ANG2), a widely used linear LRP1-binding peptide. Indocyanine green (ICG)-labeled KS-487 and ANG2 were subcutaneously administered to mice, and their biodistribution was assessed at 24, 48, and 72 h by using in vivo imaging. ICG-KS-487 and ICG-ANG2 displayed comparable brain permeability and nearly identical time-course profiles. Notably, ICG-KS-487 demonstrated greater brain selectivity, defined as the ratio of brain to liver accumulation at 72 h. No adverse effects, including weight loss or histopathological abnormalities in major organs, were observed in mice treated with ICG-KS-487. These findings highlight the remarkable brain-targeting properties and safety profile of KS-487, supporting its potential utility as a targeting ligand for drug delivery to treat brain-related disorders.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032433","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

Mannose-Conjugated Cholesterol Containing Lipid Nanoparticles for Active Targeted mRNA Delivery to Liver Sinusoidal Endothelial and Kupffer Cells. 甘露糖偶联胆固醇脂质纳米颗粒用于肝窦内皮细胞和库普弗细胞的活性靶向mRNA递送。

IF 3.9 2区化学

Bioconjugate Chemistry Pub Date : 2025-09-11 DOI: 10.1021/acs.bioconjchem.5c00282

Yujin Kim, Sumanta Chatterjee, Ava L Robertson, Erick D Guerrero, Amogh Vaidya, Xu Wang, Sang M Lee, Jingwen Wei, William E Miller, Lukas Farbiak, Daniel J Siegwart

{"title":"Mannose-Conjugated Cholesterol Containing Lipid Nanoparticles for Active Targeted mRNA Delivery to Liver Sinusoidal Endothelial and Kupffer Cells.","authors":"Yujin Kim, Sumanta Chatterjee, Ava L Robertson, Erick D Guerrero, Amogh Vaidya, Xu Wang, Sang M Lee, Jingwen Wei, William E Miller, Lukas Farbiak, Daniel J Siegwart","doi":"10.1021/acs.bioconjchem.5c00282","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00282","url":null,"abstract":"Lipid nanoparticle (LNP) delivery of mRNA to specific cell types is a necessary task for the development of safe and effective medicines. LNP delivery to the liver is largely driven by the binding of serum ApoE to the LNP surface, followed by subsequent uptake in LDL receptor (LDL-R)-expressing hepatocytes, thereby reducing their utility in nonhepatocyte liver diseases. Herein, we developed an active targeting strategy to overcome this limitation by incorporating mannose-conjugated cholesterol into LNPs. Since cholesterol comprises about half of all molecules in LNPs, we reasoned that it could serve as a scaffold for active targeting. Mannosylated LNPs enhance uptake into liver sinusoidal endothelial cells (LSECs) and Kupffer cells over hepatocytes following intravenous administration in mice. This process correlated with the expression of mannose receptors (CD206) in LSECs and Kupffer cells, where significantly greater LNP uptake and functional mRNA delivery occurred in CD206+ cells. Higher activity and selectivity could be endowed by reducing the hydrophobic acyl chain length in poly(ethylene glycol) (PEG) lipids to induce faster PEG shedding in systemic circulation and increase LNP surface-accessible mannose, thereby increasing binding interactions with mannose receptors on CD206+ cells and subsequent LNP uptake. The results establish that cholesterol can be employed as a ligand carrier in LNPs for enriching mRNA delivery to specific cells in vivo. We anticipate that this general strategy of cholesterol modification can be extended to other ligands and cell types in the future.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038665","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

Selective Coupling of Aminophosphole-Based Fluorophores to Unprotected Peptides through P-S Bond Formation. 氨基膦孔基荧光团通过P-S键形成与无保护肽的选择性偶联。

IF 3.9 2区化学

Bioconjugate Chemistry Pub Date : 2025-09-10 DOI: 10.1021/acs.bioconjchem.5c00342

Miyanou Rosales-Hurtado, Laure Liénart, Vladyslava Lunova, Jean-Louis Banères, Yvan Cuminal, Sébastien Clément, Jean-Alain Fehrentz, Arie Van Der Lee, Florine Cavelier, Emmanuelle Rémond

引用次数: 0

Phosphorothioate-Modified DNA Aptamer-Based PROTACs for Targeted Degradation of Estrogen Receptor α. 基于硫代磷酸酯修饰DNA适配体的protac靶向降解雌激素受体α。

IF 3.9 2区化学

Bioconjugate Chemistry Pub Date : 2025-09-09 DOI: 10.1021/acs.bioconjchem.5c00242

Daishi Watanabe, Hitomi Terauchi, Hinata Osawa, Miyako Naganuma, Genichiro Tsuji, Yosuke Demizu

{"title":"Phosphorothioate-Modified DNA Aptamer-Based PROTACs for Targeted Degradation of Estrogen Receptor α.","authors":"Daishi Watanabe, Hitomi Terauchi, Hinata Osawa, Miyako Naganuma, Genichiro Tsuji, Yosuke Demizu","doi":"10.1021/acs.bioconjchem.5c00242","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00242","url":null,"abstract":"Proteolysis-targeting chimeras (PROTACs) have emerged as a powerful modality for selectively degrading intracellular proteins via the ubiquitin-proteasome system. However, their development is often hindered by the limited availability of high-affinity small-molecule ligands, particularly for challenging targets, such as transcription factors. Aptamers─synthetic oligonucleotides with high affinity and specificity─offer a promising alternative as target-binding modules in the PROTAC design. In this study, we developed DNA aptamer-based PROTACs targeting estrogen receptor α (ERα), incorporating phosphorothioate (PS) backbone modifications to enhance nuclease resistance and cellular uptake. A series of aptamer-PROTACs with varying PS modification patterns were synthesized and conjugated to a cereblon ligand via copper-catalyzed click chemistry. Biophysical analyses demonstrated that PS modifications preserved the aptamer's secondary structure and binding affinity. Notably, both fully and partially PS-modified constructs exhibited significantly improved nuclease stability and intracellular delivery in MCF-7 cells. Western blot analysis confirmed that these modifications enhanced the ERα degradation activity, with partially modified constructs achieving a favorable balance between potency and specificity. In contrast, scrambled-sequence controls bearing full PS modification showed nonspecific degradation, underscoring the need for judicious PS positioning. Our findings highlight the utility of strategic PS modification for optimizing the pharmacological properties of aptamer-based PROTACs and provide a design framework for developing chemically stabilized nucleic acid degraders capable of targeting previously \"undruggable\" intracellular proteins.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028533","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

Nanoscintillators as Next-Generation Radiotherapeutics: Bridging Physics, Chemistry, and Oncology. 纳米闪烁体作为下一代放射治疗：连接物理、化学和肿瘤学。

IF 3.9 2区化学

Bioconjugate Chemistry Pub Date : 2025-09-04 DOI: 10.1021/acs.bioconjchem.5c00249

Kristel Bedregal-Portugal, Alexis Mercier, Sarah Stelse-Masson, Clémentine Aubrun, Hélène Elleaume, Camille Verry, Anne-Laure Bulin

{"title":"Nanoscintillators as Next-Generation Radiotherapeutics: Bridging Physics, Chemistry, and Oncology.","authors":"Kristel Bedregal-Portugal, Alexis Mercier, Sarah Stelse-Masson, Clémentine Aubrun, Hélène Elleaume, Camille Verry, Anne-Laure Bulin","doi":"10.1021/acs.bioconjchem.5c00249","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00249","url":null,"abstract":"Scintillating nanoparticles, or nanoscintillators, are a promising class of radiotherapeutic agents that present novel opportunities to enhance the efficacy and precision of conventional radiation therapy in cancer treatment. These nanoparticles possess the unique ability to convert ionizing radiation, such as X-rays, into visible light emission, which can, in turn, activate a variety of secondary therapeutic modalities, such as photodynamic therapy, within the tumor microenvironment. By enabling therapeutic mechanisms that are mechanistically distinct from those of ionizing radiation, nanoscintillators offer a multifaceted strategy to overcome tumor resistance and improve treatment outcomes. This Review aims to provide a focused exploration of the fundamental principles, design strategies, and emerging translational applications of scintillating nanoparticles in nanomedicine. Rather than present an exhaustive survey, we highlight key developments, current challenges, and future directions that define the state of this rapidly evolving field.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999284","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

Supramolecular Assembly of Stimuli-Responsive Protein-Chromophore Conjugate and Triggered Protein Delivery. 刺激反应蛋白-发色团偶联物的超分子组装和触发蛋白递送。

IF 3.9 2区化学

Bioconjugate Chemistry Pub Date : 2025-09-03 DOI: 10.1021/acs.bioconjchem.5c00340

Rajesh Khamrui, Krishna Dan, Suhrit Ghosh

{"title":"Supramolecular Assembly of Stimuli-Responsive Protein-Chromophore Conjugate and Triggered Protein Delivery.","authors":"Rajesh Khamrui, Krishna Dan, Suhrit Ghosh","doi":"10.1021/acs.bioconjchem.5c00340","DOIUrl":"https://doi.org/10.1021/acs.bioconjchem.5c00340","url":null,"abstract":"Protein delivery has emerged as a powerful therapeutic tool to treat many life-threatening diseases. In this study, we report the synthesis of a protein (Lysozyme = LYS)-supramolecular-structure-directing-unit (SSDU) conjugate using a redox-responsive self-destructive linker, its spontaneous self-assembly in water, intracellular delivery, and selective killing of cancer cells. The LYS surface has a few (on average 6) free amine groups, which were used to attach with the SSDU consisting of a hydrazide-functionalized naphthalene-diimide (NDI) chromophore through a urethane linkage, producing a LYS-NDI conjugate having 3 NDI chromophores on average per protein. LYS-NDI was further labeled with green-emitting FITC to produce LYS-NDI-FITC, which showed spontaneous self-assembly in water, producing near-spherical aggregates of ∼90 nm in size. In such an aggregated state, LYS remained in a dormant state and was protected from enzymatic degradation to a significant extent. In the presence of glutathione (GSH), cleavage of the disulfide bond in the linker produced free thiol, which initiated a cascade reaction through intramolecular nucleophilic attack on the adjacent carbamate linkage, releasing LYS in its active form. The LYS-NDI conjugate showed significantly higher cellular uptake selectively in cancer cells, which produced reactive oxygen species (ROS) leading to cell death. Neither LYS nor NDI showed such prominent cellular uptake or cell killing.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935671","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 Development of meso-Methyl-BODIPY Conjugates with Boc-seco-CBI and Cabozantinib: The Practical Challenges of Red-Light-Activated Prodrugs for Anticancer PDT. 中甲基- bodipy与Boc-seco-CBI和Cabozantinib偶联物的发展：红光激活抗癌PDT前药的实际挑战。

IF 3.9 2区化学

Bioconjugate Chemistry Pub Date : 2025-09-03 DOI: 10.1021/acs.bioconjchem.5c00343

Natalia S Kuzmina, Galina P Gribova, Elizaveta M Pnachina, Lubov V Krylova, Ekaterina A Fedotova, Irina V Balalaeva, Alexey Yu Fedorov, Vasilii F Otvagin

{"title":"The Development of meso-Methyl-BODIPY Conjugates with Boc-seco-CBI and Cabozantinib: The Practical Challenges of Red-Light-Activated Prodrugs for Anticancer PDT.","authors":"Natalia S Kuzmina, Galina P Gribova, Elizaveta M Pnachina, Lubov V Krylova, Ekaterina A Fedotova, Irina V Balalaeva, Alexey Yu Fedorov, Vasilii F Otvagin","doi":"10.1021/acs.bioconjchem.5c00343","DOIUrl":"10.1021/acs.bioconjchem.5c00343","url":null,"abstract":"Latest studies highlight boron-dipyrromethene (BODIPY) with a meso-methyl moiety as a promising photoremovable protecting group due to its activation within the phototherapeutic window. While BODIPYs inherently generate ROS and act as photosensitizers, few studies have explored combining their photouncaging capability with photodynamic therapy (PDT). Herein, we developed novel meso-methyl-BODIPY conjugates of the DNA alkylator Boc-seco-CBI and the multikinase inhibitor cabozantinib derivative activated by green or red light. To enhance the photodecaging efficiency of the conjugates, heavy atoms (Br, I) were introduced, and the boron atom was alkylated. The synthesized compounds were characterized for key photophysical and photochemical properties, including quantum yields of singlet oxygen generation, fluorescence, photolysis, and cytostatic release. It was shown that green-light irradiation of halogenated Boc-seco-CBI conjugates enabled rapid cytostatic release (<1 min), though with modest drug yields due to competing photodegradation. However, efficient uncaging of the cytostatic from the BODIPY-cabozantinib conjugate was achieved only after extended photoirradiation (∼80 min) with red light. In vitro evaluation using tumor (MDA-MB-231, A-431) and normal (HEK293) cell lines with various EGFR/c-Met expressions demonstrated that the BODIPY-cabozantinib conjugate exhibited predominant photosensitizing effects, with minimal cytostatic contribution. During this study, we encountered significant synthetic challenges in developing red-light-absorbing conjugates, coupled with their photodegradation under prolonged irradiation. Our observations reveal key considerations for developing conjugates based on meso-methyl-BODIPY that combine PDT with light-controlled drug release toward antitumor therapy.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935739","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

Cationic Peptide Conjugation Enhances Intratumoral Retention and Antitumor Efficacy of Immune Checkpoint Blockade Antibodies. 阳离子肽偶联增强免疫检查点阻断抗体瘤内滞留和抗肿瘤效果。

IF 3.9 2区化学

Bioconjugate Chemistry Pub Date : 2025-09-03 DOI: 10.1021/acs.bioconjchem.5c00257

Rashmi P Mohanty, Yuting Pan, Mae M Lewis, Melissa R Soto, Esther Y Maier, Riyad F Alzhrani, Debadyuti Ghosh

{"title":"Cationic Peptide Conjugation Enhances Intratumoral Retention and Antitumor Efficacy of Immune Checkpoint Blockade Antibodies.","authors":"Rashmi P Mohanty, Yuting Pan, Mae M Lewis, Melissa R Soto, Esther Y Maier, Riyad F Alzhrani, Debadyuti Ghosh","doi":"10.1021/acs.bioconjchem.5c00257","DOIUrl":"10.1021/acs.bioconjchem.5c00257","url":null,"abstract":"The tumor extracellular matrix (ECM) forms a net negatively charged network that interacts with and hinders the transport of molecules, partly based on electrostatic interactions. The focus on drug delivery in solid tumors has traditionally been on developing neutral charge coatings to minimize interactions with the ECM for improved transport. In contrast to prior work, we recently found a cationic peptide that interacted electrostatically with the negatively charged components of the ECM, resulting in enhanced uptake and retention of nanoparticles in the tumor ECM and tumor tissue. Based on this previous study, here, we hypothesize that the electrostatically driven interactions of the cationic peptide will improve the binding and retention of immune checkpoint blockade antibodies (ICBs), ultimately enhancing their antitumor immunogenic responses. We prepared peptide-antibody conjugates by conjugating the cationic peptide to anti-Cytotoxic T-Lymphocyte Antigen 4 (α-CTLA4) and anti-Programmed cell Death Ligand-1 (α-PD-L1) ICBs using copper-free click chemistry. We confirmed an average of 1-2 peptides per antibody. The cationic peptide electrostatically interacted with the net negatively charged tumor ECM and improved the binding of the antibodies to the tumor ECM without affecting their ability to recognize their antigens. Modifying the antibodies with cationic peptides reduced the systemic exposure of the antibodies and did not induce treatment-related toxicities. The conjugation of ICBs with cationic peptides improved their retention in the tumor microenvironment, resulting in improved antitumor efficacy compared to unconjugated ICBs. These results suggest that leveraging simple electrostatic interactions between cationic peptide anchors and the tumor microenvironment can ultimately improve the antitumor efficacy of immune checkpoint blockade antibodies.","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935644","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