International Journal of Nanomedicine (Nov 2022)
An Oxygen-Sufficient Nanoplatform for Enhanced Imaging-Guided Microwave Dynamic Therapy Against Hypoxic Tumors
Abstract
Rui Yang,1 Jiayan Huang,1 Min Liao,1 Jianbo Huang,1 Binyang Gao,1 Huan Zhang,1 Jie Zhou,1 Jinshun Xu,2 Qiang Lu1 1Department of Ultrasound, Laboratory of Ultrasound Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Ultrasound Medical Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Qiang Lu, Department of Ultrasound, Laboratory of Ultrasound Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Tel/Fax +86 13882175090, Email [email protected] Jinshun Xu, Ultrasound Medical Center, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People’s Republic of China, Tel/Fax +86 18708491127, Email [email protected]: Microwave dynamic therapy (MDT) as a novel reactive oxygen species (ROS)-based therapeutic modality has been explored as a promising modality for cancer treatment. However, the intrinsic hypoxic tumor microenvironment (TME) restricted the effectiveness of the MDT. The aim of this study is to develop an oxygen-sufficient nanoplatform with multi-modal imaging capability for enhanced MDT against hypoxic tumors.Methods and Materials: The liquid perfluorocarbon-based nanoplatform PFP@IR780@O2 was constructed by the phospholipid hydration and sonication method. Then, the characteristics, intracellular uptake process, and subcellular localization of PFP@IR780@O2 were verified. Additionally, the abilities of ROS generation, the anti-hypoxia capability, multi-mode imaging capabilities, and MDT efficacy of the nanoplatform were evaluated via in vitro and in vivo experiments. Finally, the in vivo biocompatibility and toxicity were also evaluated.Results: The prepared nanoparticles PFP@IR780@O2 exhibited suitable size, improved stability, elevated dissolved oxygen level, enhanced cellular uptake, and mitochondria targeting capacity. Additionally, PFP@IR780@O2 demonstrated in vitro and in vivo multimodal imaging capabilities involving ultrasound, fluorescence, and photoacoustic imaging. In vivo studies also indicated that nanoparticles were safe and capable of accumulating in the tumor site after intravenous injection. Furthermore, the PFP@IR780@O2 nanoplatform mediated MDT could effectively alleviate the hypoxic TME, and elevate ROS concentration, thereby resulting in significant tumor growth inhibition.Conclusion: Overall, the oxygen-sufficient nanoplatform with multi-bimodal imaging capability demonstrated improved MDT efficiency, indicating a promising strategy for treating hypoxic tumors.Keywords: nanomedicine, perfluorocarbon, reactive oxygen species, tumor hypoxia relief
