Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India.
Department of Developmental Biology and Genetics, Indian Institute of Science, Bangalore 560012, India.
Inorg Chem. 2024 Sep 16;63(37):17249-17262. doi: 10.1021/acs.inorgchem.4c03083. Epub 2024 Sep 5.
Using the principle of "Magic Bullet", a cisplatin-derived platinum(IV) prodrug heterobimetallic complex, -[Pt(NH)Cl{Ru(tpy-BODIPY)(tpy-COO)}(biotin)]Cl (, ), having two axial ligands, namely, biotin as water-soluble B-vitamin for enhanced cellular uptake and a BODIPY-ruthenium(II) (, ) photosensitizer having ,,-donor tpy (4'-phenyl-2,2':6',2″-terpyridine) bonded to boron-dipyrromethene (BODIPY), is developed as a "Platin Bullet" for targeted photodynamic therapy (PDT). exhibited intense absorption near 500 nm and emission near 513 nm (λ = 488 nm) in a 10% dimethyl sulfoxide-Dulbecco's phosphate-buffered saline medium (pH 7.2). The BODIPY complex on light activation generates singlet oxygen as the reactive oxygen species (ROS) giving a quantum yield (Φ) of ∼0.64 from 1,3-diphenylisobenzofuran experiments. exhibited preferential cellular uptake in cancer cells over noncancerous cells. The dichlorodihydrofluorescein diacetate assay confirmed the generation of cellular ROS. Confocal images revealed its mitochondrial internalization. showed submicromolar photocytotoxicity in visible light (400-700 nm) in A549 and multidrug-resistant MDA-MB-231 cancer cells. It remained nontoxic in the dark and less toxic in nontumorigenic cells. Cellular apoptosis and alteration of the mitochondrial membrane potential were evidenced from the respective Annexin V-FITC/propidium iodide assay and JC-1 dye assay. A wound healing assay using A549 cells and revealed inhibition of cancer cell migration, highlighting its potential as an antimetastatic agent.
利用“魔弹”原理，设计并合成了一种顺铂衍生的铂（IV）前药杂双金属配合物-[Pt(NH 3 )Cl{Ru(tpy-BODIPY)(tpy-COO)}(biotin)]Cl（1），其中两个轴向配体分别为生物素和 BODIPY-钌（II）（2）光敏剂。生物素作为水溶性维生素 B 以增强细胞摄取，BODIPY-钌（II）（2）光敏剂的配体是具有 ，，-供体 tpy（4′-苯基-2,2′:6′,2″-三联吡啶）的硼二吡咯甲烷（BODIPY），作为一种“铂弹”用于靶向光动力疗法（PDT）。1 在 10%二甲基亚砜-Dulbecco's 磷酸盐缓冲盐水介质（pH 7.2）中在近 500nm 处有强烈吸收，在近 513nm（λ=488nm）处有发射。BODIPY 配合物在光激活下产生单线态氧作为活性氧物种（ROS），通过 1,3-二苯基异苯并呋喃实验得到的量子产率（Φ）约为 0.64。1 在癌细胞中的摄取明显优于非癌细胞。二氯二氢荧光素二乙酸酯测定法证实了细胞 ROS 的产生。共焦图像显示其线粒体内化。1 在 A549 和多药耐药 MDA-MB-231 癌细胞中的可见光（400-700nm）下表现出亚微摩尔的光细胞毒性。在黑暗中它保持非毒性，在非肿瘤细胞中毒性更小。通过各自的 Annexin V-FITC/碘化丙啶测定法和 JC-1 染料测定法证实了细胞凋亡和线粒体膜电位的改变。使用 A549 细胞和 1 的划痕愈合试验表明抑制了癌细胞迁移，突出了其作为抗转移剂的潜力。
