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Biotin-Pt(IV)-Ru(II)-Boron-Dipyrromethene Prodrug as "Platin Bullet" for Targeted Chemo- and Photodynamic Therapy.

Arpan BeraAmrita NepaliaAarti UpadhyayDeepak Kumar SainiAkhil R Chakravarty
Published in: Inorganic chemistry (2024)
Using the principle of "Magic Bullet", a cisplatin-derived platinum(IV) prodrug heterobimetallic Pt(IV)-Ru(II) complex, cis,cis,trans -[Pt(NH 3 ) 2 Cl 2 {Ru(tpy-BODIPY)(tpy-COO)}(biotin)]Cl 2 ( Pt-Ru-B , 2 ), having two axial ligands, namely, biotin as water-soluble B-vitamin for enhanced cellular uptake and a BODIPY-ruthenium(II) ( Ru-B , 1 ) photosensitizer having N , N , N -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). Pt-Ru-B exhibited intense absorption near 500 nm and emission near 513 nm (λ ex = 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 Δ ) of ∼0.64 from 1,3-diphenylisobenzofuran experiments. Pt-Ru-B 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. Pt-Ru-B 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 Pt-Ru-B revealed inhibition of cancer cell migration, highlighting its potential as an antimetastatic agent.
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