Programmably Controllable Delivery of Metastable Ferrous Ions for Multiscale Dynamic Imaging Guided Photothermal Primed Chemodynamic Therapy,Advanced Materials

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Programmably Controllable Delivery of Metastable Ferrous Ions for Multiscale Dynamic Imaging Guided Photothermal Primed Chemodynamic Therapy
Advanced Materials ( IF 27.4 ) Pub Date : 2023-03-04 , DOI: 10.1002/adma.202210876
Xinming Zhang ₁ , Song Lin ₁ , Feng Zhao ₁ , Jing Zhang ₁ , Shan Lei ₁ , Fang Bai ₁ , Qiang Liu ₁ , Jiayingzi Wu ₁ , Ting He ₁ , Peng Huang ₁ , Jing Lin ₁

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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 (Fe²⁺) 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–Fe²⁺ complex with a precise stoichiometry of 1:1 to steadily maintain the valence state of Fe²⁺. The CFNPs can achieve pH-responsive visualization and accurate Fe²⁺ 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–Fe²⁺ complex delivery for photothermal primed Fe²⁺ release, thus achieving CDT of tumors. By leveraging multiscale dynamic imaging technologies, the complicated spatiotemporal release of Fe²⁺ 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.

中文翻译：

用于多尺度动态成像引导光热引发化学动力学治疗的亚稳态亚铁离子的可编程控制输送

金属调节细胞死亡策略被广泛研究用于抗肿瘤治疗，例如铜死亡、铁死亡和化学动力学疗法（CDT）。毫无疑问，癌细胞中金属离子水平的准确和特异性升高是提高其治疗指数的关键。在此，开发了一种基于克罗科染料（Croc）-亚铁离子（Fe ^{2+ ）纳米探针（CFNP）的可编程可控输送系统，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，可以以1:1的精确化学计量形成Croc-Fe ^{2+络合物，从而稳定地维持Fe}²⁺的价态。CFNP 可以实现 pH 响应可视化和准确的 Fe ²⁺在“酸性和近红外（NIR）光”的“双键”刺激下，在癌组织中释放。酸性肿瘤微环境激活 CFNP 的近红外荧光/光声成像和光热特性。随后，在外源近红外光下，CFNP 能够在体内准确地可视化 Croc-Fe ²⁺复合物的递送，以实现光热引发的 Fe ²⁺释放，从而实现肿瘤的 CDT。利用多尺度动态成像技术，以可编程可控的方式勾画出Fe ²⁺复杂的时空释放，并揭示肿瘤pH水平、光热效应和CDT的多米诺骨牌效应，从而赋予治疗全景的定制反馈疾病微环境。

更新日期：2023-03-04

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