Biotin–Pt(IV)–Ru(II)–Boron–Dipyrromethene\nProdrug as “Platin Bullet” for Targeted Chemo- and Photodynamic\nTherapy

Using the principle of “Magic\nBullet”, a cisplatin-derived\nplatinum(IV) prodrug heterobimetallic <b>Pt(IV)–Ru(II)</b> complex, <i>cis,cis,trans</i>-[Pt(NH<sub>3</sub>)<sub>2</sub>Cl<sub>2</sub>{Ru(tpy–BODIPY)(tpy–COO)}(biotin)]Cl<sub>2</sub> (<b>Pt–Ru–B</b>, <b>2</b>), having\ntwo axial ligands, namely, biotin as water-soluble B-vitamin for enhanced\ncellular uptake and a BODIPY–ruthenium(II) (<b>Ru–B</b>, <b>1</b>) photosensitizer having <i>N</i>,<i>N</i>,<i>N</i>-donor tpy (4′-phenyl-2,2′:6′,2″-terpyridine)\nbonded to boron-dipyrromethene (BODIPY), is developed as a “Platin\nBullet” for targeted photodynamic therapy (PDT). <b>Pt–Ru–B</b> exhibited intense absorption near 500 nm and emission near 513 nm\n(λ<sub>ex</sub> = 488 nm) in a 10% dimethyl sulfoxide-Dulbecco’s\nphosphate-buffered saline medium (pH 7.2). The BODIPY complex on light\nactivation generates singlet oxygen as the reactive oxygen species\n(ROS) giving a quantum yield (Φ<sub>Δ</sub>) of ∼0.64\nfrom 1,3-diphenylisobenzofuran experiments. <b>Pt–Ru–B</b> exhibited preferential cellular uptake in cancer cells over noncancerous\ncells. The dichlorodihydrofluorescein diacetate assay confirmed the\ngeneration of cellular ROS. Confocal images revealed its mitochondrial\ninternalization. <b>Pt–Ru–B</b> showed submicromolar\nphotocytotoxicity in visible light (400–700 nm) in A549 and\nmultidrug-resistant MDA-MB-231 cancer cells. It remained nontoxic\nin the dark and less toxic in nontumorigenic cells. Cellular apoptosis\nand alteration of the mitochondrial membrane potential were evidenced\nfrom the respective Annexin V-FITC/propidium iodide assay and JC-1\ndye assay. A wound healing assay using A549 cells and <b>Pt–Ru–B</b> revealed inhibition of cancer cell migration, highlighting its potential\nas an antimetastatic agent.