1. Hypoxia-triggered single molecule probe for high-contrast NIR II/PA tumor imaging and robust photothermal therapy
- Author
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Zhihong Sun, Guanjun Deng, Lintao Cai, Wenjun Li, Sanpeng Li, Ping Gong, Zhang Jiali, Meng Xiaoqing, and Lihua Zhou
- Subjects
Fluorescence-lifetime imaging microscopy ,Medicine (miscellaneous) ,Mice, Nude ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Theranostic Nanomedicine ,Photoacoustic Techniques ,Nitroreductase ,Molecule ,hypoxia-triggered ,PA imaging ,Animals ,Hypoxia ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Mice, Inbred BALB C ,Chemistry ,Photothermal effect ,Optical Imaging ,NIR II fluorescence imaging ,Hyperthermia, Induced ,Neoplasms, Experimental ,Photothermal therapy ,Nitroreductases ,Phototherapy ,021001 nanoscience & nanotechnology ,Fluorescence ,In vitro ,0104 chemical sciences ,Disease Models, Animal ,single molecule probe ,Biophysics ,0210 nano-technology ,Molecular probe ,activatable photothermal therapy ,Research Paper - Abstract
Hypoxia is a common characteristic of solid tumors. This important feature is associated with resistance to radio-chemotherapy, which results in poor prognosis and probability of tumor recurrence. Taking advantage of background-free NIR II fluorescence imaging and deeper-penetrating photoacoustic (PA) imaging, we developed a hypoxia-triggered and nitroreductase (NTR) enzyme-responsive single molecule probe for high-contrast NIR II/PA tumor imaging and hypoxia-activated photothermal therapy (PTT), which will overcome cellular resistance during hypoxia. Methods: The single molecule probe IR1048-MZ was synthesized by conjugating a nitro imidazole group as a specific hypoxia trigger with an IR-1048 dye as a NIR II/PA signal reporter. We investigated the NIR II fluorescence, NIR absorbance and photothermal effect in different hypoxia conditions in vitro, and performed NIR II/PA tumor imaging and hypoxia-activated photothermal therapy in mice. Results: This versatile molecular probe IR1048-MZ not only realized high-contrast tumor visualization with a clear boundary by NIR II fluorescence imaging, but also afforded deep-tissue penetration at the centimeter level by 3D PA imaging. Moreover, after being activated by NTR that is overexpressed in hypoxic tumors, the probe exhibited a significant photothermal effect for curative tumor ablation with no recurrence. Conclusions: We have developed the first hypoxia-triggered and NTR enzyme-responsive single molecule probe for high-contrast NIR II/PA tumor imaging and hypoxia-activated photothermal therapy. By tracing the activity of NTR, IR1048-MZ may be a promising contrast agent and theranostic formulation for other hypoxia-related diseases (such as cancer, inflammation, stroke, and cardiac ischemia).
- Published
- 2018