Bioconjugate Chemistry最新文献

{"title":"Positron Emission Tomography and Optical Imaging to Monitor Bioorthogonal Diels-Alder Click Chemistry of Trastuzumab with a Porphyrin.","authors":"Sara R D Gamelas, Shayla Shmuel, Cristina Simó, Alex Vanover, João P C Tomé, Augusto C Tomé, Leandro M O Lourenço, Patrícia M R Pereira","doi":"10.1021/acs.bioconjchem.5c00056","DOIUrl":"10.1021/acs.bioconjchem.5c00056","url":null,"abstract":"<p><p>Click chemistry to allow <i>in vivo</i> conjugation of a fluorophore porphyrin (Por)-tetrazine (Tz) with the human epidermal growth factor receptor 2 (HER2)-targeting trastuzumab conjugated with trans-cyclooctene (TCO) is described here. <i>In vitro</i> experiments confirmed successful click reactions between Por-Tz and trastuzumab-TCO and validated preserved trastuzumab immunoreactivity (no significant change in HER2 binding, <i>p</i> > 0.05). Positron emission tomography (PET) of [⁸⁹Zr]Zr-DFO-trastuzumab-TCO demonstrated 17.1 ± 2.9% injected dose per gram of tumor at 48 h postinjection. Optical imaging showed an ∼10-fold increase in the click group for Por-Tz when compared with Por-Tz alone. This preclinical data demonstrate a pretargeted approach for dual PET and optical imaging of HER2-expressing tumors.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1013-1020"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951372","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":"","authors":"Desoshree Ghosh,&nbsp;Sagar Bag and Priyadarsi De*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 5","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.5c00097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144360954","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":"","authors":"Jinjin Zhao,&nbsp;Xiaorou Wang,&nbsp;Haiguang Zhang,&nbsp;Qunmei Zhang,&nbsp;DeYing Bo,&nbsp;Hua Zhong,&nbsp;Luyang Jiao*,&nbsp;Hongchang Yuan* and Guangjian Lu*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 5","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.5c00001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144360958","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 5","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/bcv036i005_1937752","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144390715","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":"","authors":"Yanchen Li,&nbsp;Jin Wang,&nbsp;Tingting Liu,&nbsp;Junyu Zhang,&nbsp;Yuanyuan Shan* and Jie Zhang*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 5","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.5c00116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144390718","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":"Bioorthogonally Activatable Photosensitizer for NIR Fluorescence Imaging-Guided Highly Selective Elimination of Senescent Tumor Cells and Chemotherapy Enhancement.","authors":"Yun Feng, Zifan Zhu, Shirui Zhao, Xingyu Jiang, Wen Zhang, Zhiai Xu","doi":"10.1021/acs.bioconjchem.5c00109","DOIUrl":"10.1021/acs.bioconjchem.5c00109","url":null,"abstract":"<p><p>Chemotherapy is a primary modality in cancer treatment, but it may induce cellular senescence, which in turn triggers the release of senescence-associated secretory phenotypes (SASPs) that promote tumor growth and metastasis. To selectively identify senescent cells and mitigate their negative impact on cancer therapy, herein, we have developed a β-galactosidase (β-Gal)-activated and self-immobilizing photosensitizer CyGF-DBCO-T. This photosensitizer can be selectively activated and fluorescently label proteins in situ within senescent cells, enabling near-infrared (NIR) fluorescence imaging-guided photodynamic therapy (PDT) for the precise ablation of these cells. First, we developed an activatable NIR fluorescent probe CyGF-N₃ that can specifically in situ label senescent cells. Subsequently, DBCO-T with free radicals underwent a bioorthogonal click reaction with activated CyGF-N₃ in senescent cells to generate the photosensitizer CyO-DBCO-T. Under light irradiation, CyO-DBCO-T generated singlet oxygen (¹O₂) in situ, thereby enabling precise PDT with fluorescence guidance and photoactivation. Both CyGF-N₃ and DBCO-T were encapsulated in biotinylated liposomes (CyGF-N₃@LIP-B and DBCO-T@LIP-B), which enhanced their water solubility, tumor targeting, and in vivo circulation time. This promoted the accumulation of the probes in senescent tumor cells, thus enabling intense fluorescence imaging of tumor senescence regions in mice and enhancing the efficacy of PDT. This dual-module strategy, guided by fluorescence imaging for PDT, has achieved selective identification and precise ablation of senescent tumor cells in a chemotherapy-induced senescence model, effectively alleviating chemotherapy resistance and suppressing tumor growth.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1066-1078"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950737","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":"GSH-Responsive Heterodimeric Dual-Targeted Nanomedicine Modulates EMT to Conquer Paclitaxel-Induced Invasive Breast Cancer Metastasis.","authors":"Ying Chen, Yao Chen, Hong Xu, Jianan Liu, Yan Wang, Yingjie Zeng, Hongyu Chen, Yuening Cao, Chen Sun, Xian Ge, Tingting Zhang, Xiaoke Shi, Xiujun Cao, Yilan Liu, Bo Ren, Tianbao Wang, Jun Lu","doi":"10.1021/acs.bioconjchem.5c00145","DOIUrl":"10.1021/acs.bioconjchem.5c00145","url":null,"abstract":"<p><p>Paclitaxel (PTX), although effective against primary breast cancer, presents formidable clinical challenges due to severe toxicity and pro-metastatic potential, a critical concern as distant metastasis causes 90% of breast cancer-related deaths. To address these limitations, we designed and prepared a tumor microenvironment-responsive nanoprodrug, PTX-SS-3'HPT@RGD-HA NPs, that engineered RGD peptide-modified hyaluronic acid (HA) nanocarriers encapsulating the antimetastatic 3'-hydroxy pterostilbene (3'HPT) and PTX heterodimer linked by a glutathione (GSH)-cleavable disulfide bond. These nanoparticles targeting CD44 and αvβ receptors overexpressed in aggressive breast cancer cells and synergized enhanced permeability and retention effects with receptor-mediated endocytosis, facilitating superior tumor-specific drug deposition and GSH-activated payload release <i>in vitro</i> and <i>in vivo</i>. Moreover, PTX-SS-3'HPT@RGD-HA NPs achieved excellent tumor growth inhibition while mitigating systemic toxicity and metastatic risks in 4T1 tumor-bearing mice. Mechanistically, 3'HPT counteracted PTX-induced epithelial-mesenchymal transition by downregulating MMP-9/N-cadherin and restoring E-cadherin expression, thereby neutralizing PTX-triggered pro-metastatic effects. This study pioneers a dual-targeted, toxicity-shielding nanoplatform that simultaneously improves therapeutic efficacy and addresses chemotherapy-driven metastasis, offering a revolutionary strategy for managing highly invasive breast cancer.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1098-1112"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951309","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":"Tumor Cell Membrane Biomimetic Mesoporous Silicon Materials in Combination with PD-L1 Knockout Achieved through the CRISPR/Cas9 System for Targeted and Immunotherapeutic Purposes.","authors":"Jinjin Zhao, Xiaorou Wang, Haiguang Zhang, Qunmei Zhang, DeYing Bo, Hua Zhong, Luyang Jiao, Hongchang Yuan, Guangjian Lu","doi":"10.1021/acs.bioconjchem.5c00001","DOIUrl":"10.1021/acs.bioconjchem.5c00001","url":null,"abstract":"<p><p>Nanoparticle-based drug delivery systems, which enable the effective and targeted delivery of chemotherapeutic drugs to tumors, have revolutionized cancer therapy. Mesoporous silicon materials (MSN) have emerged as promising candidates for drug delivery due to their unique properties. The therapeutic efficacy can be significantly enhanced when treatments exhibit both targeting and antiphagocytic properties. In this study, cell membranes extracted from B16-F10 cells were used to encapsulate carboplatin (CBP)-loaded MSN via physical extrusion. Additionally, we intratumorally injected a plasmid containing the CRISPR/Cas9 system to achieve PD-L1 knockout, thereby reactivating the immune system. The cell membrane coating endowed the CBP@MSN with excellent slow-release capability and cytocompatibility. Enhanced tumor cell uptake of CBP@MSN@M was observed due to homologous targeting by cancer cell membranes. Moreover, CBP@MSN@M demonstrated enhanced antitumor efficacy in vivo and promoted the proliferation of immune cells. Finally, the antitumor effect was further improved by the knockout of PD-L1 within the tumor microenvironment. These results suggest that the newly prepared CBP@MSN@M, combined with PD-L1 knockout, holds significant potential as an effective therapeutic approach for treating tumors.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"971-979"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952149","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":"Super-Sensitive Chemiluminescent Probe for the Detection of Caspase-3 Activity.","authors":"Rozan Tannous, Chi Zhang, Doron Shabat","doi":"10.1021/acs.bioconjchem.5c00151","DOIUrl":"10.1021/acs.bioconjchem.5c00151","url":null,"abstract":"<p><p>Caspase-3 is a pivotal enzyme in the apoptosis pathway that is responsible for executing programmed cell death through the cleavage of key cellular proteins. Existing fluorescence-based probes for caspase-3 detection suffer from limitations such as background noise from tissue autofluorescence and light scattering, reducing their sensitivity and real-time imaging capabilities. To overcome these limitations, we developed a chemiluminescent probe, Ac-DEVD-CL, that enables the highly sensitive and selective detection of caspase-3 activity. Upon caspase-3-mediated cleavage, the probe undergoes a self-immolative reaction that triggers a chemiluminescent signal, allowing real-time monitoring of the enzymatic activity. Probe Ac-DEVD-CL demonstrated an exceptionally high turn-on response, with a 5000-fold increase in the chemiluminescent signal upon enzymatic activation. The probe exhibited notable specificity for caspase-3, with minimal cross-reactivity toward other biologically relevant proteases and tumor-associated enzymes. Additionally, inhibition studies using the caspase-3 inhibitor confirmed that the probe's activation is exclusively mediated by caspase-3. A direct comparison with the commercially available fluorescent probe revealed that probe Ac-DEVD-CL offers significantly improved sensitivity, achieving a signal-to-noise ratio 380-fold higher and a limit of detection 100-fold lower. These results establish probe Ac-DEVD-CL as a highly effective tool for detecting caspase-3 activity with superior precision. Finally, we validated the probe's utility in imaging apoptosis in live cells. In 4T1 breast cancer cells treated with cisplatin, Ac-DEVD-CL generated a strong chemiluminescent signal, with a three-order-of-magnitude enhancement compared to untreated cells. Overall, the probe Ac-DEVD-CL demonstrates a significant improvement in detection sensitivity, providing a powerful and versatile chemiluminescent probe for real-time imaging of caspase-3 activity. Its exceptional sensitivity and selectivity could make it a valuable tool for cancer research, drug discovery, and therapeutic monitoring.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"1113-1120"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954395","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":"Redesigning Ibuprofen for Improved Oral Delivery and Reduced Side Effects.","authors":"Szilvia H Toth, Anca D Stoica, Cristian Sevcencu","doi":"10.1021/acs.bioconjchem.4c00558","DOIUrl":"10.1021/acs.bioconjchem.4c00558","url":null,"abstract":"<p><p>Ibuprofen (IBP) is one of the most widely used nonsteroidal anti-inflammatory drugs (NSAIDs). Being well-known for its efficacy, long history of use, and reduced adverse events compared to other NSAIDs, IBP is authorized as an analgesic and antipyretic drug. IBP's mechanism of action consists of inhibiting cyclooxygenases, which are crucial oxidoreductases in prostaglandin synthesis and generation of inflammation and pain. However, despite being effective and relatively safe, IBP can still induce a dose-dependent toxicity which manifests mainly in the gastrointestinal system as ulcerations and altered mucosal blood flow and cytotoxicity characterized by mitochondrial dysfunction and increased membrane permeability in enterocytes and hepatocytes. Therefore, ongoing research is performed to improve the IBP's activity and treatment outcome, and one way to achieve such improvements is through reducing IBP's toxicity by designing less harmful but still effective novel IBP conjugates. The aim of this review is to summarize the latest achievements with IBP conjugation techniques that created such valuable IBP formulations less toxic than but as effective as the parent drug.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":" ","pages":"893-913"},"PeriodicalIF":4.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951032","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}