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BODIPY 标记的铂(II)姜黄素配合物用于内质网靶向红光 PDTPDT。

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

出版信息

Inorg Chem. 2022 Jan 24;61(3):1335-1348. doi: 10.1021/acs.inorgchem.1c02745. Epub 2022 Jan 6.

DOI:10.1021/acs.inorgchem.1c02745
PMID:34990135
Abstract

[Pt(RB)(Cur)]NO (), [Pt(IRB)(Cur)]NO (), and [Pt(L)(Cur)]NO (), 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). and 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 and , respectively, in 10% DMSO-DPBS. (Φ, 0.27) and (Φ, 0.40) generated singlet oxygen in red light (λ = 642 nm) as evidenced from 1,3-diphenylisobenzofuran (DPBF) titrations. The formation of O 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: 1.3-6.9 μM, red light; 7.2-12.8 μM, 400-700 nm visible light]. The emissive 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.

摘要

[Pt(RB)(Cur)]NO (), [Pt(IRB)(Cur)]NO (), 和 [Pt(L)(Cur)]NO (),其中 HCur 是姜黄素,L 是 1-苯甲基-2-(2-吡啶基)苯并咪唑,RB 和 IRB 分别是标记在 L 上的红光活性非碘和二碘-BODIPY,被合成并进行了表征,并研究了它们的抗癌活性 (BODIPY,硼二吡咯甲烷)。 在 10%二甲基亚砜 (DMSO)-杜氏磷酸盐缓冲盐水 (DPBS) 中, 和 分别显示出在 615-635nm 处的 BODIPY 中心吸收带,以及各自在 445 和 492nm 处的姜黄素带。 在 10%DMSO-DPBS 中, 和 分别观察到 723nm 和 845nm 的发射带。 (Φ,0.27)和 (Φ,0.40)在红光(λ = 642nm)下生成单线态氧,这从 1,3-二苯基异苯并呋喃(DPBF)滴定中得到证实。 从机制 pUC19 DNA 光裂研究中证实了 BODIPY 从姜黄素中生成 O 和 HO 的形成。 BODIPY 配合物在 A549、HeLa 和 MDA-MB-231 细胞中表现出光细胞毒性,而在黑暗中毒性较小[IC:1.3-6.9μM,红光;7.2-12.8μM,400-700nm 可见光]。 发光的 显示出内质网 (ER) 的定位。 用 Annexin-V/荧光素异硫氰酸酯 (FITC)/碘化丙啶 (PI) 测定法和红光中的 Fluo-4 AM 测定法中的绿色荧光证实了细胞凋亡死亡,这是由于 ER 应激引起的,线粒体功能障碍用 A549 细胞中的 5,5,6,6'-四氯-1,1',3,3'-四乙基苯并咪唑基咔啉碘化物 (JC-1) 测定法证实。

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