ROS-Responsive Nanosystem Targeted Co-Delivery YC-1 and Regorafenib to Alleviate Hypoxia Enhancing Hepatocellular Carcinoma Therapy
Liming Song,1– 3 Yahui Wu,1– 3 Senfeng Zhao,1– 3 Yin Liu,1– 3 Zhipu Liu,1– 3 Yunpeng Zhai,1– 3 Jiahui Cao,1– 3 Yaning Xia,4 Ruopeng Liang,1– 3 Weijie Wang,1– 3 Rongtao Zhu,1– 3 Binghua Sun,5 Yupeng Shi,4 Yuling Sun1– 3 1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospita...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2025-07-01
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| Series: | International Journal of Nanomedicine |
| Subjects: | |
| Online Access: | https://www.dovepress.com/ros-responsive-nanosystem-targeted-co-delivery-yc-1-and-regorafenib-to-peer-reviewed-fulltext-article-IJN |
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| Summary: | Liming Song,1– 3 Yahui Wu,1– 3 Senfeng Zhao,1– 3 Yin Liu,1– 3 Zhipu Liu,1– 3 Yunpeng Zhai,1– 3 Jiahui Cao,1– 3 Yaning Xia,4 Ruopeng Liang,1– 3 Weijie Wang,1– 3 Rongtao Zhu,1– 3 Binghua Sun,5 Yupeng Shi,4 Yuling Sun1– 3 1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Institute of Hepatobiliary and Pancreatic Diseases, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 3Zhengzhou Basic and Clinical Key Laboratory of Hepatopancreatobiliary Diseases, Zhengzhou, 450052, People’s Republic of China; 4Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 5Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of ChinaCorrespondence: Yuling Sun, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China, Email ylsun@zzu.edu.cn Yupeng Shi, Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China, Email shiyup@zzu.edu.cnPurpose: The current treatment of hepatocellular carcinoma (HCC) is confronted with anoxic drug resistance and significant side effects. To address these issues, a Reactive Oxygen Species (ROS)-responsive and targeted nano drug delivery system named REG/YC-1@PTP-RGD NPs (RYP-RGD NPs) was designed for the co-delivery of Regorafenib (REG) and the hypoxia inhibitor 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1).Methods: RYP-RGD NPs were fabricated through the self-assembly method. A series of techniques, such as transmission electron microscopy (TEM), UV-visible spectroscopy, and others, were employed to characterize their properties. In Vitro investigations encompassed drug release assays, cytotoxicity evaluations using Cell Counting Kit-8 (CCK-8) and other methods, cell uptake experiments, and Western blot analysis. In vivo, the biodistribution of RYP-RGD NPs was tracked by IVIS imaging, and their antitumor efficacy and biosafety were assessed in a HepG2 tumor-bearing mouse model with histological staining and biochemical analysis.Results: RYP-RGD NPs exhibited a spherical morphology with an appropriate size and excellent dispersion. They demonstrated ROS-triggered drug release behavior. In vitro studies revealed good tumor-targeting ability, enhanced cytotoxicity against HCC cells, and the downregulation of hypoxia-inducible factor-1α (HIF-1α) by YC-1. In vivo experiments showed improved tumor targeting, significant inhibition of tumor growth, and lower toxicity compared to single drugs.Conclusion: The successfully developed RYP-RGD NPs offer a novel strategy for HCC treatment. They enhance drug targeting, synergistically boost the therapeutic effect, and maintain biosafety, showing great potential for clinical translation.Keywords: drug delivery, reactive oxygen species, hypoxia, regorafenib, nanocarrier |
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| ISSN: | 1178-2013 |