Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, China.
Adv Mater. 2023 Jun;35(25):e2210876. doi: 10.1002/adma.202210876. Epub 2023 May 1.
Metallomodulation cell death strategies are extensively investigated for antitumor therapy, such as cuproptosis, ferroptosis, and chemodynamic therapy (CDT). Undoubtedly, the accurate and specific elevation of metal ions levels in cancer cells is key to boosting their therapeutic index. Herein, a programmably controllable delivery system based on croconium dye (Croc)-ferrous ion (Fe ) nanoprobes (CFNPs) is developed for multiscale dynamic imaging guided photothermal primed CDT. The Croc, with kinds of electron-rich iron-chelating groups, can form the Croc-Fe complex with a precise stoichiometry of 1:1 to steadily maintain the valence state of Fe . The CFNPs can achieve pH-responsive visualization and accurate Fe release in cancerous tissues under the coactivation of "dual-key" stimulation of "acidity and near-infrared (NIR) light". The acidic tumor microenvironment actuates NIR fluorescence/photoacoustic imaging and photothermal properties of CFNPs. Sequentially, under exogenous NIR light, the CFNPs enable in vivo accurate visualization of Croc-Fe complex delivery for photothermal primed Fe release, thus achieving CDT of tumors. By leveraging multiscale dynamic imaging technologies, the complicated spatiotemporal release of Fe is sketched in a programmably controllable manner, and the domino effect of tumor pH level, photothermal effect, and CDT is also revealed, endowing customized feedback of the therapeutic panorama within the disease microenvironment.
金属调节细胞死亡策略被广泛研究用于抗肿瘤治疗，如铜死亡、铁死亡和化学动力学治疗（CDT）。毫无疑问，准确和特异性地提高癌细胞中的金属离子水平是提高其治疗指数的关键。在此，开发了一种基于 Croconium 染料（Croc）-亚铁离子（Fe ）纳米探针（CFNPs）的可编程控制递药系统，用于多尺度动态成像引导光热引发的 CDT。Croc 具有多种富电子铁螯合基团，可与 Fe 形成精确化学计量比为 1:1 的 Croc-Fe 配合物，以稳定地维持 Fe 的价态。CFNPs 可以在“酸度和近红外（NIR）光”的“双钥匙”协同激活下，在癌组织中实现 pH 响应可视化和准确的 Fe 释放。酸性肿瘤微环境激活 CFNPs 的 NIR 荧光/光声成像和光热特性。随后，在外源性 NIR 光下，CFNPs 能够实现体内 Croc-Fe 配合物递药的精确可视化，用于光热引发的 Fe 释放，从而实现肿瘤的 CDT。通过利用多尺度动态成像技术，以可编程控制的方式描绘了复杂的时空 Fe 释放，还揭示了肿瘤 pH 水平、光热效应和 CDT 的级联效应，在疾病微环境内为治疗全景提供定制化的反馈。
