ROS-Responsive Nanosystem Targeted Co-Delivery YC-1 and Regorafenib to Alleviate Hypoxia Enhancing Hepatocellular Carcinoma Therapy

作者：Liming Song, Yahui Wu, Senfeng Zhao, Yin Liu, Zhipu Liu, Yunpeng Zhai, Jiahui Cao, Yaning Xia, Ruopeng Liang, Weijie Wang, Rongtao Zhu, Binghua Sun, Yupeng Shi, Yuling Sun · 发表于：International Journal of Nanomedicine · 年份：2025 · DOI：10.2147/ijn.s518120 · 被引用次数：6 · 研究领域：Nanoplatforms for cancer theranostics、Cancer, Hypoxia, and Metabolism、Nanoparticle-Based Drug Delivery

Purpose: 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 comp...