Oxoplatin-B, a cisplatin-based platinum(IV) complex with photoactive BODIPY for mitochondria specific “chemo-PDT” activity

• Published in: Journal of inorganic biochemistry Vol. 223; p. 111526
• Main Authors: Bera, Arpan, Gautam, Srishti, Raza, Md Kausar, Kondaiah, Paturu, Chakravarty, Akhil R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2021
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Antineoplastic Agents - radiation effects; Apoptosis - drug effects; Benzoates - chemical synthesis; Benzoates - pharmacology; Benzoates - radiation effects; Bioinorganic chemistry; Boron Compounds - chemical synthesis; Boron Compounds - pharmacology; Boron Compounds - radiation effects; Boron-dipyrromethene; Cattle; Cell Line, Tumor; Coordination Complexes - chemical synthesis; Coordination Complexes - pharmacology; Coordination Complexes - radiation effects; DNA - drug effects; DNA Cleavage - drug effects; Drug Screening Assays, Antitumor; Humans; Light; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; Mitochondrial localization; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - pharmacology; Photosensitizing Agents - radiation effects; Platinum; Platinum - chemistry; Platinum - radiation effects; Prodrugs - chemical synthesis; Prodrugs - pharmacology; Prodrugs - radiation effects; Singlet oxygen; Singlet Oxygen - metabolism; Mitochondrial localization; Singlet oxygen; Photodynamic therapy; Boron-dipyrromethene; Bioinorganic chemistry; Platinum
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2021.111526

Oxoplatin-B, a platinum(IV) complex [Pt(NH3)2Cl2(L1)(OH)] (1) of 4-methylbenzoic acid (HL1) functionalized with 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) was prepared, characterized and its antitumor activity studied. [Pt(NH3)2Cl2(L2)(OH)] (2) of 4-methylbenzoic acid (HL2) was studied as a control. Complex 1 showed an absorption band at 500 nm (ɛ = 4.34 × 104 M−1 cm−1) and an emission band at 515 nm (λex = 488 nm, ΦF = 0.64) in 1% dimethyl sulfoxide/Dulbecco's Modified Eagle's Medium (pH = 7.2). Visible light-induced (400–700 nm) generation of singlet oxygen was evidenced from 1,3-diphenylisobenzofuran titration study. Complex 1 showed photo-induced cytotoxicity in visible light (400–700 nm, 10 J cm−2) against human breast cancer (MCF-7), cervical cancer (HeLa) and lung cancer (A549) cells (IC50: 1.1–3.8 μM) while being less toxic in normal cells. Confocal imaging showed mitochondrial localization with additional evidence from platinum content from isolated mitochondria and 5,5,6,6′-tetrachloro-1,1′,3,3′ tetraethylbenzimi-dazoylcarbocyanine iodide (JC-1) assay. Cellular apoptosis was observed from Annexin-V-FITC (fluorescein isothiocyanate)/propidium iodide assay. Synopsis: Oxoplatin-B, the platinum(IV) complex [Pt(NH3)2Cl2(L1)(OH)] (1) having boron-dipyrromethene appended 4-methylbenzoic acid (HL1) shows mito-targeted apoptotic photocytotoxicity in green light in human breast (MCF-7), cervical (HeLa) and lung (A549) cancer cells forming singlet oxygen, while being non-toxic in dark and less cytotoxic in normal lung epithelial (HPL1D) cells. [Display omitted] •Oxoplatin-B complex showed apoptotic photocytotoxicity in visible light.•Confocal imaging showed mitochondria-specific localization of the Pt(IV) complex.•Complex is a photochemotherapeutic agent releasing boron-dipyrromethene and cisplatin.•Mitochondrial membrane potential disruption was observed by the complex.•Prodrug uses combinatorial approach of photo-activated and chemo-photodynamic therapy.