Department of Radiology , The First Affiliated Hospital of China Medical University , Shenyang 110001 , China.
Laboratory of Controllable Preparation and Application of Nanomaterials, Laboratory of Cryogenics, Technical Institute of Physics and Chemistry , Chinese Academy of Sciences , Beijing 100190 , China.
ACS Appl Mater Interfaces. 2020 Feb 19;12(7):8016-8029. doi: 10.1021/acsami.9b22802. Epub 2020 Feb 10.
Arsenic trioxide (ATO) is effective in the treatment of hematological malignancies and solid tumors. However, its toxicity and side effects are severe, posing an obstacle in its clinical application. A controlled-release ATO carrier with mitochondrial targeting was constructed in this study. The safety and efficacy in vitro were investigated using a hemolysis test, cytotoxicity, proliferation, migration, apoptosis, and other changes in cell behavior. The safety and efficacy were further evaluated in vivo by hematoxylin-eosin staining, terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling staining, and blood testing in tumor-bearing mice. Immunohistochemically and western blotting experiments were conducted to explore the mechanism of combination therapy of material-based chemotherapy and microwave hyperthermia in vitro. We demonstrated that the nano-zirconia (ZrO) loading platform may be used to administer the ATO, with local precision-controlled release and mitochondrial targeting. Furthermore, we showed the safety of this approach for delivering high doses of ATO. In addition, we explored this new method in combination with in vitro microwave heat therapy, providing a potentially novel intravenous approach to chemotherapy. We described a new non-invasive treatment that improved the efficacy of ATO chemotherapy against hepatocellular carcinoma through nano-ZrO carriers.
三氧化二砷（ATO）在治疗血液系统恶性肿瘤和实体瘤方面具有疗效。然而，其毒性和副作用严重，成为其临床应用的障碍。本研究构建了一种具有线粒体靶向的 ATO 控释载体。通过溶血试验、细胞毒性、增殖、迁移、凋亡等细胞行为变化，研究了其体外的安全性和疗效。通过荷瘤小鼠的苏木精-伊红染色、末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记染色和血液检测，进一步评估了其体内的安全性和疗效。通过免疫组织化学和蛋白质印迹实验，探讨了材料化疗联合微波热疗的体外联合治疗机制。结果表明，纳米氧化锆（ZrO）载药平台可用于 ATO 的给药，实现局部精准控释和线粒体靶向。此外，我们还证明了这种方法递送高剂量 ATO 的安全性。此外，我们还探索了这种新方法与体外微波热疗的联合应用，为化疗提供了一种潜在的新型静脉内治疗方法。我们描述了一种新的非侵入性治疗方法，通过纳米 ZrO 载体提高了 ATO 化疗治疗肝癌的疗效。
