Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
Analyst. 2019 Nov 21;144(22):6681-6688. doi: 10.1039/c9an01746a. Epub 2019 Oct 10.
The anticancer mechanism of NO is difficult to study owing to its short lifetime and high reactivity. Thus, a theranostic anticancer NO donor assembled with NO on-demand release abilities, accurate lysosome location capabilities and signal feedback behavior was developed. Profiting from the theranostic properties, the specific mechanism was comprehensively studied. Spectral and cell imaging studies revealed that the as prepared NO donors could release NO in solution or within cancer cells. Fluorescence co-dyeing experiments demonstrated that Mo-Nap-NO entered lysosomes specifically and disrupted them after being triggered by light. Upon irradiation with 460 nm visible light, both the donors demonstrated considerable in vitro anticancer effects. A further mechanistic study showed that after entering the lysosome and being triggered by 460 nm irradiation, NO ruptured the lysosome, resulting in the release of cathepsin D into the cytosol, which activated the caspase3 mediated apoptosis pathway.
由于其半衰期短、反应活性高，NO 的抗癌机制难以研究。因此，开发了一种具有按需释放 NO 能力、准确溶酶体定位能力和信号反馈行为的治疗性抗癌 NO 供体。得益于治疗学特性，全面研究了特定机制。光谱和细胞成像研究表明，所制备的 NO 供体可以在溶液或癌细胞内释放 NO。荧光共染实验表明，Mo-Nap-NO 特异性进入溶酶体，并在被光触发后破坏它们。在 460nm 可见光照射下，供体均表现出相当大的体外抗癌作用。进一步的机制研究表明，进入溶酶体并在 460nm 照射下被触发后，NO 会破坏溶酶体，导致组织蛋白酶 D 释放到细胞质中，从而激活 caspase3 介导的细胞凋亡途径。
