Department of Polymers and Functional Materials, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, Uttar Pradesh, India.
ACS Appl Bio Mater. 2023 Sep 18;6(9):3778-3789. doi: 10.1021/acsabm.3c00440. Epub 2023 Aug 16.
It is an established fact that cancer is one of the most serious public health issues after coronary artery disease. Thus, exploring more effective and efficient therapeutic protocols over the traditional chemotherapeutic strategy is imperative to improving cancer survivorship and patient quality of life. In this respect, recent reports on molecularly engineered -substituted BODIPY have shown remarkable effects as a photoresponsive CO-releasing platform for the on-demand release of CO to treat cancer. Herein, we designed and synthesized two -substituted BODIPY photoresponsive CO-releasing molecules (photoCORMs). These BODIPY derivatives were tethered to a phenoxymethylpyridine moiety and oligoethylene glycol to maintain a hydrophilic-hydrophobic balance and improved cell permeability. The cell imaging experiments demonstrated that oligoethylene glycol containing photoCORM-1 efficiently internalized and preferentially localized at the mitochondria. To understand the mechanistic aspect of preferential localization into the mitochondria, live cell imaging was also carried out. Photorelease of CO was directly monitored by the inline IR spectroscopic technique. Finally, in vitro cytotoxicity and apoptosis assays on MDA-MB-231 cell lines clearly showed that photoCORM-1 induced apoptosis-mediated cell killing on account of photoreleased CO, which otherwise showed insignificant toxicity even at a very high concentration of ∼50 μM.
癌症是继冠心病之后最严重的公共卫生问题之一，这是一个既定的事实。因此，探索比传统化疗策略更有效和高效的治疗方案对于提高癌症患者的生存率和生活质量至关重要。在这方面，最近关于分子工程化取代 BODIPY 的报告显示，作为一种光响应性 CO 释放平台，具有显著的效果，可按需释放 CO 来治疗癌症。在此，我们设计并合成了两种取代 BODIPY 光响应性 CO 释放分子（photoCORM）。这些 BODIPY 衍生物连接到苯氧甲基吡啶部分和聚乙二醇上，以维持亲水-亲脂平衡和提高细胞通透性。细胞成像实验表明，含有聚乙二醇的 photoCORM-1 能够有效地内化，并优先定位于线粒体。为了了解优先定位于线粒体的机制方面，还进行了活细胞成像。通过在线红外光谱技术直接监测 CO 的光释放。最后，在 MDA-MB-231 细胞系上进行的体外细胞毒性和细胞凋亡实验清楚地表明，photoCORM-1 通过光释放的 CO 诱导凋亡介导的细胞杀伤，而 photoCORM-1 本身即使在非常高的浓度（约 50 μM）下也没有显示出明显的毒性。
