Iridium Complex-Loaded Sorafenib Nanocomposites for Synergistic Chemo-photodynamic Therapy of Hepatocellular Carcinoma

作者：Weinire Abuduwaili, Xiang Wang, An-Tian Huang, Jialei Sun, Ru-Chen Xu, Guangcong Zhang, Zhiyong Liu, Fu Wang, Changfeng Zhu, Taotao Liu, Ling Dong, Ji‐Min Zhu, Shu‐Qiang Weng, Yuhao Li, Xizhong Shen · 发表于：ACS Applied Materials & Interfaces · 年份：2022 · DOI：10.1021/acsami.2c07247 · 被引用次数：23 · 研究领域：Nanoplatforms for cancer theranostics、Photodynamic Therapy Research Studies、Hepatocellular Carcinoma Treatment and Prognosis

Although sorafenib, a multi-kinase inhibitor, has provided noteworthy benefits in patients with hepatocellular carcinoma (HCC), the inevitable side effects, narrow therapeutic window, and low bioavailability seriously affect its clinical application. To be clinically distinctive, innovative drugs must meet the needs of reaching tumor tissues and cause limited side effects to normal organs and tissues. Recently, photodynamic therapy, utilizing a combination of a photosensitizer and light irradiation, was selectively accumulated at the tumor site and taken up effectively via inducing apoptosis or necrosis of cancer cells. In this study, a nano-chemo-phototherapy drug was fabricated to compose an iridium-based photosensitizer combined with sorafenib (IPS) via a self-assembly process. Compared to the free iridium photosensitizer or sorafenib, the IPS exhibited significantly improved therapeutic efficacy against tumor cells because of the increased cellular uptake and the subsequent simultaneous release of sorafenib and generation of reactive oxygen species production upon 532 nm laser irradiation. To evaluate the effect of synergistic treatment, cytotoxicity detection, live/dead staining, cell proliferative and apoptotic assay, and Western blot were performed. The IPS exhibited sufficient biocompatibility by hemolysis and serum biochemical tests. Also, the results suggested that IPS significantly inhibited HCC cell proliferation and promoted cell apoptosis. More importantly, mark...