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

Abstract

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, marked anti-tumor growth effects via inhibiting cell proliferation and promoting tumor cell death were observed in an orthotopic xenograft HCC model. Therefore, our newly proposed nanotheranostic agent for combined chemotherapeutic and photodynamic therapy notably improves the therapeutic effect of sorafenib and has the potential to be a new alternative option for HCC treatment.

• Authors: Weinire Abuduwaili, Xiang Wang, An-Tian Huang, Jia-Lei Sun, Ru-Chen Xu, Guang-Cong Zhang, Zhi-Yong Liu, Fu Wang, Chang-Feng Zhu, Tao-Tao Liu, Ling Dong, Ji-Min Zhu, Shu-Qiang Weng, Yuhao Li, Xi-Zhong Shen
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 14 Issue 33 Pg. 37356-37368 (Aug 24 2022) ISSN: 1944-8252 [Electronic] United States
• PMID: 35951459 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Photosensitizing Agents
• Iridium
• Sorafenib

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis
• Carcinoma, Hepatocellular (pathology)
• Cell Line, Tumor
• Cell Proliferation
• Humans
• Iridium (pharmacology)
• Liver Neoplasms (pathology)
• Nanocomposites (therapeutic use)
• Photochemotherapy
• Photosensitizing Agents (pharmacology, therapeutic use)
• Sorafenib (therapeutic use)