研究动态
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BASHY 染料是高效的脂滴靶向光敏剂,可通过脂质过氧化诱导铁死亡。

BASHY Dyes Are Highly Efficient Lipid Droplet-Targeting Photosensitizers that Induce Ferroptosis through Lipid Peroxidation.

发表日期:2023 Nov 10
作者: Maria J S A Silva, Yiyi Zhang, Robin Vinck, Fábio M F Santos, João P M António, Lisa Gourdon-Grünewaldt, Charlotte Zaouter, Annie Castonguay, Shunmoogum A Patten, Kevin Cariou, Francisco Boscá, Francisco Nájera, Jesús F Arteaga, Gilles Gasser, Uwe Pischel, Pedro M P Gois
来源: BIOCONJUGATE CHEMISTRY

摘要:

铁死亡是一种铁依赖性脂质过氧化驱动的细胞死亡机制,也是根除癌细胞的有前景的治疗靶点。在这项研究中,我们发现硼酸衍生的水杨腙(BASHY)染料是高效的单线态氧光敏剂(PS;ΦΔ高达0.8),可诱导光动力疗法引发的铁死亡。性能最佳的 BASHY 染料对人多形性胶质母细胞瘤 U87 细胞系表现出高光毒性,IC50 值在低纳摩尔范围内 (4.40 nM),并且具有显着的光毒性指数 (PI > 22,700)。重要的是,BASHY 染料被证明会在脂滴 (LD) 中积累,并且这种细胞内分隔对于增强光毒性和通过脂质过氧化诱导铁死亡至关重要。使用体内斑马鱼模型(Danio rerio)验证了该平台的安全性和光毒性。
Ferroptosis is an iron-dependent lipid-peroxidation-driven mechanism of cell death and a promising therapeutic target to eradicate cancer cells. In this study, we discovered that boronic acid-derived salicylidenehydrazone (BASHY) dyes are highly efficient singlet-oxygen photosensitizers (PSs; ΦΔ up to 0.8) that induce ferroptosis triggered by photodynamic therapy. The best-performing BASHY dye displayed a high phototoxicity against the human glioblastoma multiform U87 cell line, with an IC50 value in the low nanomolar range (4.40 nM) and a remarkable phototoxicity index (PI > 22,700). Importantly, BASHY dyes were shown to accumulate in lipid droplets (LDs) and this intracellular partition was found to be essential for the enhanced phototoxicity and the induction of ferroptosis through lipid peroxidation. The safety and phototoxicity of this platform were validated using an in vivo zebrafish model (Danio rerio).