Wei Tang1, Zhen Yang2, Liangcan He1, Liming Deng1, Parinaz Fathi1, Shoujun Zhu3, Ling Li1, Bo Shen4, Zhantong Wang1, Orit Jacobson1, Jibin Song5, Jianhua Zou1, Ping Hu6, Min Wang6, Jing Mu1, Yaya Cheng1, Yuanyuan Ma1, Longguang Tang1, Wenpei Fan7, Xiaoyuan Chen8. 1. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, 20892, USA. 2. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, 20892, USA. beijinyz@126.com. 3. State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 130012, Changchun, P.R. China. 4. Institute of Radiation Medicine, Fudan University, 200032, Shanghai, P.R. China. 5. MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, 350116, Fuzhou, P.R. China. 6. State Key Laboratory of High-Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 200050, Shanghai, P.R. China. 7. State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, 210009, Nanjing, P.R. China. wenpei.fan@cpu.edu.cn. 8. Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, 117597, Singapore, Singapore. chen.shawn@nus.edu.sg.
Abstract
The outcome of radiotherapy is significantly restricted by tumor hypoxia. To overcome this obstacle, one prevalent solution is to increase intratumoral oxygen supply. However, its effectiveness is often limited by the high metabolic demand for O2 by cancer cells. Herein, we develop a hybrid semiconducting organosilica-based O2 nanoeconomizer pHPFON-NO/O2 to combat tumor hypoxia. Our solution is twofold: first, the pHPFON-NO/O2 interacts with the acidic tumor microenvironment to release NO for endogenous O2 conservation; second, it releases O2 in response to mild photothermal effect to enable exogenous O2 infusion. Additionally, the photothermal effect can be increased to eradicate tumor residues with radioresistant properties due to other factors. This "reducing expenditure of O2 and broadening sources" strategy significantly alleviates tumor hypoxia in multiple ways, greatly enhances the efficacy of radiotherapy both in vitro and in vivo, and demonstrates the synergy between on-demand temperature-controlled photothermal and oxygen-elevated radiotherapy for complete tumor response.
The outcome of radiotherapy is significantly restricted by pan class="Disease">tumor hypoxia. To overcome this obstacle, one prevalent solution is to increase intratumoral oxygen supply. However, its effectiveness is often limited by the high metabolic demand for O2 by cancer cells. Herein, we develop a hybrid semiconducting organosilica-based O2 nanoeconomizer pHPFON-NO/O2 to combat tumor hypoxia. Our solution is twofold: first, the pHPFON-NO/O2 interacts with the acidic tumor microenvironment to release NO for endogenous O2 conservation; second, it releases O2 in response to mild photothermal effect to enable exogenous O2 infusion. Additionally, the photothermal effect can be increased to eradicate tumor residues with radioresistant properties due to other factors. This "reducing expenditure of O2 and broadening sources" strategy significantly alleviates tumor hypoxia in multiple ways, greatly enhances the efficacy of radiotherapy both in vitro and in vivo, and demonstrates the synergy between on-demand temperature-controlled photothermal and oxygen-elevated radiotherapy for complete tumor response.