{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:59:05Z","timestamp":1787029145368,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Research Funds for the Central Universities of China","award":["2042021kf1033"],"award-info":[{"award-number":["2042021kf1033"]}]},{"name":"Fundamental Research Funds for the Central Universities of China","award":["T2023042"],"award-info":[{"award-number":["T2023042"]}]},{"name":"Fundamental Research Funds for the Central Universities of China","award":["X2024ZZ001"],"award-info":[{"award-number":["X2024ZZ001"]}]},{"name":"Excellent Young and Middle-aged Scientific and Technological Innovation Team Program of Hubei Province","award":["2042021kf1033"],"award-info":[{"award-number":["2042021kf1033"]}]},{"name":"Excellent Young and Middle-aged Scientific and Technological Innovation Team Program of Hubei Province","award":["T2023042"],"award-info":[{"award-number":["T2023042"]}]},{"name":"Excellent Young and Middle-aged Scientific and Technological Innovation Team Program of Hubei Province","award":["X2024ZZ001"],"award-info":[{"award-number":["X2024ZZ001"]}]},{"name":"Research and Development Fund of Wuchang University of Technology","award":["2042021kf1033"],"award-info":[{"award-number":["2042021kf1033"]}]},{"name":"Research and Development Fund of Wuchang University of Technology","award":["T2023042"],"award-info":[{"award-number":["T2023042"]}]},{"name":"Research and Development Fund of Wuchang University of Technology","award":["X2024ZZ001"],"award-info":[{"award-number":["X2024ZZ001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In recent years, the near-infrared (NIR) fluorescence theranostic system has garnered increasing attention for its advantages in the simultaneous diagnosis- and imaging-guided delivery of therapeutic drugs. However, challenges such as strong background fluorescence signals and rapid metabolism have hindered the achievement of sufficient contrast between tumors and surrounding tissues, limiting the system\u2019s applicability. This study aims to integrate the pegylation strategy with a tumor microenvironment-responsive approach. A novel esterase-activated EPR strategy prodrug, OBHSA-PEG-DCM, was designed. This prodrug links OBHSA, a protein degrader capable of efficient ER\u03b1 protein degradation, to the PEG-modified fluorescent group (dicyanomethylene-4H-pyran, DCM) via an ester bond. This integration facilitates targeted drug delivery and enhances the retention of the fluorescent group within the tumor, allowing distinct in vivo tumor imaging periods. Experimental results show that, benefiting from overexpressed esterase in cancer cells, OBHSA-PEG-DCM can be efficiently hydrolyzed, releasing OBHSA and pegylated DCM. OBHSA demonstrated potent inhibition against MCF-7 cells (IC50 = 1.09 \u03bcM). Simultaneously, pegylated DCM exhibited remarkable in vivo imaging capabilities, lasting up to 12 days in mice, due to the enhanced permeability and retention (EPR) effect. OBHSA-PEG-DCM holds promise as a theranostic agent for ER\u03b1-positive breast cancer, offering both therapeutic and diagnostic capabilities. Importantly, this study highlights the utility of pegylated NIR fluorophores for long-circulating drug delivery systems, addressing current challenges in achieving high-contrast tumor imaging and effective targeted drug release.<\/jats:p>","DOI":"10.3390\/molecules30020305","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T07:35:47Z","timestamp":1736840147000},"page":"305","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pegylated NIR Fluorophore-Conjugated OBHSA Prodrug for ER\u03b1-Targeted Theranostics with Enhanced Imaging and Long-Term Retention"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6867-1893","authenticated-orcid":false,"given":"Xiaohua","family":"Wang","sequence":"first","affiliation":[{"name":"School of Environmental Ecology and Biological Engineering, Wuhan Institute of Technology, Wuhan 430205, China"},{"name":"College of Life Sciences, Wuchang University of Technology, Wuhan 430223, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilan","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chune","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China"},{"name":"State Key Laboratory of Virology and Biosafety, Frontier Science Center for Immunology and Metabolism, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5591-1893","authenticated-orcid":false,"given":"Guoyuan","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Environmental Ecology and Biological Engineering, Wuhan Institute of Technology, Wuhan 430205, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8498-063X","authenticated-orcid":false,"given":"Hai-Bing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China"},{"name":"State Key Laboratory of Virology and Biosafety, Frontier Science Center for Immunology and Metabolism, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1186\/bcr78","article-title":"Estrogen receptor transcription and transactivation Estrogen receptor alpha and estrogen receptor beta: Regulation by selective estrogen receptor modulators and importance in breast cancer","volume":"2","author":"Katzenellenbogen","year":"2000","journal-title":"Breast Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1023\/A:1026114501364","article-title":"Ligand-induced regulation of ER\u03b1 and ER\u03b2 is indicative of human breast cancer cell proliferation","volume":"81","author":"Power","year":"2003","journal-title":"Breast Cancer Res. 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