Chavda Jaydeepsinh, Siwach Arjun, Sabharwal Sudhir, Janaagal Anu, Bhatia Dhiraj, Gupta Iti
Department of Chemistry, IIT Gandhinagar, Palaj, Gandhinagar, Gujarat 382055, India.
Department of Biological Engineering, IIT Gandhinagar, Palaj, Gandhinagar, Gujarat 382055, India.
ACS Med Chem Lett. 2024 Sep 13;15(12):2115-2120. doi: 10.1021/acsmedchemlett.4c00275. eCollection 2024 Dec 12.
Lysosomal enzymes and high accumulation of lipid droplets are associated with breast cancer. The lysosomes and lipid droplets were monitored by BODIPYs, acting as autophagy activators in cancer cells. and were synthesized and characterized by Mass, UV-visible, fluorescence, and NMR spectroscopies. In BODIPYs, the effect of carbazole groups was reflected by the large Stokes shifts (2143-1651 cm) and red fluorescence. BODIPYs generated ROS and induced autophagy in triple negative breast cancer cells (MDA-MB-231) under white light. Confocal experiments revealed that and preferentially colocalized in lysosomes and lipid droplets. Autophagic lysosomes and lipid droplets released Ca ions in the cytoplasm, which was evident with blue fluorescence of Fura-2M dye. In combination with an autophagy inhibitor, displayed excellent photocytotoxicity (5.57 μM) on triple negative breast cancer cells under white light. This work demonstrates the potential of BODIPYs as theranostic agents for the photodynamic therapy against TNBC.
溶酶体酶和脂滴的高积累与乳腺癌相关。通过BODIPY对溶酶体和脂滴进行监测,BODIPY在癌细胞中作为自噬激活剂。[此处原文缺失两个物质名称]通过质谱、紫外可见光谱、荧光光谱和核磁共振光谱进行合成和表征。在BODIPY中,咔唑基团的作用通过大的斯托克斯位移(2143 - 1651厘米)和红色荧光体现。BODIPY在白光下在三阴性乳腺癌细胞(MDA - MB - 231)中产生活性氧并诱导自噬。共聚焦实验表明[此处原文缺失两个物质名称]优先共定位于溶酶体和脂滴中。自噬溶酶体和脂滴在细胞质中释放钙离子,这通过Fura - 2M染料的蓝色荧光得以显现。与自噬抑制剂联合使用时,[此处原文缺失物质名称]在白光下对三阴性乳腺癌细胞表现出优异的光细胞毒性(5.57 μM)。这项工作证明了BODIPY作为用于三阴性乳腺癌光动力治疗的诊疗试剂的潜力。