Precisely activating ferroptosis by Fe(II)-triggered drug release for enhanced cancer therapy

在2022财年，主要进行了铁响应性体外释药系统的开发和优化工作。设计并合成了几种肟酯模型。考察了其对水溶液中Fe2+的稳定性和反应活性。ESI-MS谱证实了Fe2+活化释放的反应机理和反应产物。在课题组工作的基础上，合成了荧光菁染料和肿瘤靶向部分cRGD，并设计和合成了基于反应的新型功能荧光传感器，用于检测生物标本中与疾病相关的微小变化，如pH和酶。由于菁染料的水溶性差，在水溶液中容易聚集，阻碍了其在生物应用中的生物相容性。我正试图通过将几个磺酸盐基团引入到苯并吲哚部分的菁染料中来开发水溶性近红外pH响应型菁染料。含有两个或三个阴离子基团的染料即使在没有表面活性剂或有机溶剂的水溶液中也表现出更好的水溶性。有趣的是，我发现染料在水溶液中的聚集纳米颗粒大小依赖于pH值的变化，这有望用于改善EPR效应，用于体内靶向和特异性肿瘤成像。此外，今年还进行了一些关于酶反应探针的细胞实验，以与其他研究人员合作。

In the year of FY2022, the development and optimization of iron(II)-responsive drug release system in vitro was mainly conducted. Several oxime ester models were designed and synthesized. The stability and reactivity towards Fe2+ in aqueous solutions were evaluated. The proposed reaction mechanism and reaction product for the Fe2+-activated release were confirmed by ESI-MS spectra. Fluorescent cyanine dye and tumor-targeting moiety cRGD were synthesized by following the reported work of our research group.My research also focused on the design and synthesis of novel reaction-based functional fluorescent sensors to detect the diseases-related tiny changes in biological specimens such as pH, and enzymes. Due to the poor water-solubility and easily aggregation of cyanine dyes in aqueous solutions which hamper their biocompatibility in biological application. I am trying to develop the water-soluble Near-infrared pH-responsive cyanine dyes through introduction of several sulfonate groups to the benzoindole moiety of cyanine dyes. The dyes containing two or three anionic groups exhibited better water-solubility even in aqueous solutions without surfactant or organic solvents. Interestingly, I found that the aggregation nanoparticle size of dye in aqueous solutions was changed dependent on pH values which is promising to be used for the improved EPR effect for targeted and specific tumor imaging in vivo models.Besides, some cell experiments about enzyme-responsive probes for the cooperations with other researcher were conducted in this year.