期刊
ADVANCED FUNCTIONAL MATERIALS
卷 32, 期 23, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202200016
关键词
methylglyoxal; nanotheranostics; NIR-II fluorescence imaging; precise cancer therapy; tumor metabolism
类别
资金
- National Natural Science Foundation of China [22074043, 22174047, 22177068]
- Science and Technology Commission of Shanghai Municipality [20142202800]
- fundamental research funds from the central universities [m20190319]
In this study, a near-infrared II (NIR-II) fluorescence nanotheranostic system activated by methylglyoxal (MGO) was developed for cancer therapy. The system showed highly specific activation in tumors and achieved combinatory therapy through photothermal and photodynamic effects.
Second near-infrared (NIR-II) fluorescence imaging with deep tissue-penetration ability holds remarkable potential for cancer diagnosis. However, clinical translation of NIR-II fluorescence imaging-based cancer treatment is severely restricted by the low signal-to-background ratio due to insufficient tumor specificity of fluorophores. In this study, it is hypothesized that methylglyoxal (MGO), an intermediate metabolite of tumor glycolysis could be used as a potent biomarker for triggering NIR-II fluorescence imaging-guided cancer theranostic. For proof-of-concept, first a MGO-activatable NIR-II fluorescence probe is developed, and then MGO-responsive dual lock-and-key nanotheranostics by integrating the NIR-II fluorophore and a photodynamic prodrug (i.e., hexyl 5-aminolevulinic acid hydrochloride (HAL)) into one nanoparticle is engineered. The nanotheranostic can be specifically activated with tumorous MGO for NIR-II fluorescence imaging-guided combinatory cancer therapy. Upon 808 nm laser irradiation, the activated NIR-II fluorophore can generate tunable photothermal effect to trigger HAL release. Subsequently, HAL is converted to protoporphyrin IX inside the tumor cells for 655 nm laser irradiation-induced photodynamic therapy. It is demonstrated that the NIR-II fluorescence nanotheranostics is highly specifically activated in the tumor and efficiently suppressed 4T1 breast tumor growth in mouse model. The NIR-II fluorescence imaging-based nanotheranostic might imply novel insight into reactive metabolite-activatable precise therapy of tumor.
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