Iridium Tungstate Nanozyme-Mediated Hypoxic Regulation and Anti-inflammation for Duplex Imaging Guided Photothermal Therapy of Metastatic Breast Tumors
Mingcheng Wang, Yuqin Liang, Fangling Liao, Muhammad Rizwan Younis, Yue Zheng, Xiaoya Zhao, Xiyong Yu, Weisheng Guo, Dongyang Zhang
Abstract
Metastasis of breast cancer is key to poor prognosis and high mortality. However, the excess reactive oxygen species (ROS) and inflammatory response induced by photothermal therapy (PTT) further aggravate tumor metastasis. Meanwhile, the hypoxic tumor microenvironment promotes tumor cells to metastasize to distant organs. Herein, the intrinsic limitations of PTT for metastatic tumor have been addressed by fabricating polyethylene glycol modified iridium tungstate (IrWOx-PEG) nanoparticles. The as-designed IrWOx-PEG nanoparticles displayed good photothermal (PT) conversion ability for duplex photoacoustic/PT imaging guided PTT and multienzyme mimetic feature for broad-spectrum ROS scavenging. On the one hand, IrWOx-PEG effectively removed excess ROS generated during PTT and reduced inflammation. On the other hand, owing to the catalase-like activity, it preferentially triggered the catalytic production of oxygen by decomposing ROS, leading to relieving of the hypoxic microenvironment. Hence, under bimodal imaging guidance, IrWOx-PEG induced PTT completely eliminated in situ breast cancer in 4T1 tumor-bearing mice with no observable system toxicity, as well as further restricting tumor metastasis to other vital organs (lungs) by ROS scavenging, anti-inflammation, and regulating hypoxic microenvironment. We anticipate that this work will lead to new treatment strategies for other metastatic cancers.