Pegylated NIR Fluorophore-Conjugated OBHSA Prodrug for ERα-Targeted Theranostics with Enhanced Imaging and Long-Term Retention
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...
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2025-01-01
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| author | Xiaohua Wang Xiaofei Deng Lilan Xin Chune Dong Guoyuan Hu Hai-Bing Zhou |
| author_facet | Xiaohua Wang Xiaofei Deng Lilan Xin Chune Dong Guoyuan Hu Hai-Bing Zhou |
| author_sort | Xiaohua Wang |
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| description | 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’s 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 ERα protein degradation, to the PEG-modified fluorescent group (dicyanomethylene-4<i>H</i>-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 (IC<sub>50</sub> = 1.09 μM). 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 ERα-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. |
| format | Article |
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| publishDate | 2025-01-01 |
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| series | Molecules |
| spelling | doaj-art-73353f4ec00a40e3bc9cbae96e3b35e62025-01-24T13:43:30ZengMDPI AGMolecules1420-30492025-01-0130230510.3390/molecules30020305Pegylated NIR Fluorophore-Conjugated OBHSA Prodrug for ERα-Targeted Theranostics with Enhanced Imaging and Long-Term RetentionXiaohua Wang0Xiaofei Deng1Lilan Xin2Chune Dong3Guoyuan Hu4Hai-Bing Zhou5School of Environmental Ecology and Biological Engineering, Wuhan Institute of Technology, Wuhan 430205, ChinaDepartment of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, ChinaDepartment of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, ChinaDepartment of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, ChinaSchool of Environmental Ecology and Biological Engineering, Wuhan Institute of Technology, Wuhan 430205, ChinaDepartment of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, ChinaIn 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’s 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 ERα protein degradation, to the PEG-modified fluorescent group (dicyanomethylene-4<i>H</i>-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 (IC<sub>50</sub> = 1.09 μM). 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 ERα-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.https://www.mdpi.com/1420-3049/30/2/305estrogen receptorsdrug deliveryNIR fluorescence imagingprodrug conjugatespegylationesterase activation |
| spellingShingle | Xiaohua Wang Xiaofei Deng Lilan Xin Chune Dong Guoyuan Hu Hai-Bing Zhou Pegylated NIR Fluorophore-Conjugated OBHSA Prodrug for ERα-Targeted Theranostics with Enhanced Imaging and Long-Term Retention Molecules estrogen receptors drug delivery NIR fluorescence imaging prodrug conjugates pegylation esterase activation |
| title | Pegylated NIR Fluorophore-Conjugated OBHSA Prodrug for ERα-Targeted Theranostics with Enhanced Imaging and Long-Term Retention |
| title_full | Pegylated NIR Fluorophore-Conjugated OBHSA Prodrug for ERα-Targeted Theranostics with Enhanced Imaging and Long-Term Retention |
| title_fullStr | Pegylated NIR Fluorophore-Conjugated OBHSA Prodrug for ERα-Targeted Theranostics with Enhanced Imaging and Long-Term Retention |
| title_full_unstemmed | Pegylated NIR Fluorophore-Conjugated OBHSA Prodrug for ERα-Targeted Theranostics with Enhanced Imaging and Long-Term Retention |
| title_short | Pegylated NIR Fluorophore-Conjugated OBHSA Prodrug for ERα-Targeted Theranostics with Enhanced Imaging and Long-Term Retention |
| title_sort | pegylated nir fluorophore conjugated obhsa prodrug for erα targeted theranostics with enhanced imaging and long term retention |
| topic | estrogen receptors drug delivery NIR fluorescence imaging prodrug conjugates pegylation esterase activation |
| url | https://www.mdpi.com/1420-3049/30/2/305 |
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