BODIPY-Tagged Platinum(II) Curcumin Complexes for Endoplasmic Reticulum-Targeted Red Light PDT

Abstract

Metrics & More Article Recommendations * sı Supporting Information ABSTRACT: [Pt(RB)(Cur)]NO 3 (RBC), [Pt(IRB)(Cur)]NO 3 (IRBC), and [Pt(L)(Cur)]NO 3 (PBC), where HCur is curcumin, L is 1-benzyl-2-(2-pyridyl)benzimidazole, and RB and IRB are red-light-active non-iodo and diiodo-BODIPY tagged to L, respectively, were synthesized and characterized, and their anticancer activities were studied (BODIPY, boron-dipyrromethene). RBC and IRBC displayed BODIPY-centered absorption bands within 615−635 nm along with the respective curcumin bands at 445 and 492 nm in 10% dimethyl sulfoxide (DMSO)− Dulbecco's phosphate-buffered saline (DPBS). Emission bands were observed at 723 and 845 nm for RBC and IRBC, respectively, in 10% DMSO−DPBS. RBC (Φ Δ , 0.27) and IRBC (Φ Δ , 0.40) generated singlet oxygen in red light (λ = 642 nm) as evidenced from 1,3diphenylisobenzofuran (DPBF) titrations. The formation of 1 O 2 from BODIPY and HO • from the curcumin was evidenced from the mechanistic pUC19 DNA photocleavage studies. The BODIPY complexes showed photocytotoxicity in A549, HeLa, and MDA-MB-231 cells while being less toxic in the dark [IC 50 : 1.3−6.9 μM, red light; 7.2−12.8 μM, 400−700 nm visible light]. The emissive RBC displayed localization in the endoplasmic reticulum (ER).Apoptotic cell death was evidenced from the Annexin-V/fluorescein isothiocyanate (FITC)/propidium iodide (PI) assay and green fluorescence in red light in the Fluo-4 AM assay due to ER stress, and mitochondrial dysfunction was evidenced from the 5,5,6,6′tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) assay in A549 cells.

Computational Analysis of the Behavior of BODIPY Decorated Monofunctional Platinum(II) Complexes in the Dark and under Light Irradiation

“…Boron dipyrromethanes (BODIPYs) are fluorescent dyes that have attracted considerable attention due to their excellent photochemical properties − and have been widely used in combination with Pt­(II) chemotherapeutic agents also because the introduction of the Pt atom in the BODIPYs structure should increase their efficacy in generating singlet oxygen enhancing the intersystem crossing, thereby favoring spin–orbit coupling. ,− …”

A Platinum(II) Boron‐dipyrromethene Complex for Cellular Imaging and Mitochondria‐targeted Photodynamic Therapy in Red Light

“…They were utilized in the received form. Ligand HAcac‐RB and the complexes DPP‐Pt and Acacplatin‐RB were synthesized using modified reported procedures [26,28] . The instruments and methods used for biological characterization and other studies are described as Supporting Information (SI).…”

“…[21][22][23][24][25] To this effect, we have reported BODIPY conjugates of platinum(II) complexes of curcumin demonstrating generation of singlet oxygen in moderate yield on red light photoirradiation showing IC 50 values within 1.3-6.9 μM in A549 (lung epithelial cancer cells) and MDA-MB231 (breast cancer cells) cancer cells while remaining inactive in dark. [26] To develop new types of photoactive platins showing redlight PDT activity, our group has recently reported Maloplatin-B, having a methyl malonyl chloride derivative of BODIPY as a bidentate O,O-donor ligand. [27] This complex behaved as a potential "chemo-PDT" agent showing photocytotoxicity in the range of 1.6-2.4 μM in A549 and HeLa cells.…”

“…Their remarkable photophysical properties showing intense absorption at relatively long wavelength, high stability, facile high yield synthesis with tunable core, and desirable optoelectronic properties have enabled their use as photosensitizers in PDT [21–25] . To this effect, we have reported BODIPY conjugates of platinum(II) complexes of curcumin demonstrating generation of singlet oxygen in moderate yield on red light photoirradiation showing IC 50 values within 1.3‐6.9 μM in A549 (lung epithelial cancer cells) and MDA‐MB231 (breast cancer cells) cancer cells while remaining inactive in dark [26] …”

Red light active Pt(iv)–BODIPY prodrug as a mitochondria and endoplasmic reticulum targeted chemo-PDT agent

“…21 For therapeutic application, the PS is highly preferred to be active in the PDT spectral window (600–800 nm) where the light has deep tissue penetration ability with diminished scattering and could annihilate cell auto-fluorescence interference. 22,23 With that objective we have modified our approach by functionalizing cisplatin with a red-light active BODIPY moiety which is active in the PDT therapeutic window. In addition, the BODIPY ligand designed by us, being a strong light-harvesting organic dye, offers various desirable properties that include high photostability, redox inactivity within the biological redox window, a tunable core for suitable absorption and emission properties, enabling the platinum–BODIPY conjugate for bioimaging and PDT applications.…”