Curley Rhianne C, Arturo Arellano-Reyes Ruben, McPherson James N, McKee Vickie, Keyes Tia E
School of Chemical Sciences, National Centre for Sensor Research, Dublin City University, Dublin, Ireland.
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.
Chemistry. 2024 Dec 18;30(71):e202403149. doi: 10.1002/chem.202403149. Epub 2024 Nov 9.
The uptake and phototoxicity of a family of BODIPY-perylene charge transfer dyads are compared in live cancer and non-cancer cell lines to evaluate their performance in imaging and photodynamic therapy (PDT). The impact of iodination and mesylation of the meso position of the compounds on their optical properties, cell uptake and toxicity are compared. Notably, across all derivatives the probes were minimally dark toxic up to 50 μM, (the maximum concentration tested), but exhibited outstanding phototoxicity with nanomolar IC values and impressive phototoxic indices (PI, ratio of dark IC to light IC), with best performance for the mesylated iodinated derivative MB2PI, which had a PI of >218 and >8.9 in MCF-7 cells and tumour spheroids respectively. This is significantly higher than non-iodinated analogue MB2P in MCF-7 cells with an observed PI of >109 and slightly higher than MB2PI in spheroids with a PI of >8. This compound also showed interesting emission spectral variation with localisation that responded to stimulation of inflammation. Additional studies confirmed efficient singlet oxygen generation by the BODIPYs, suggesting a Type II mechanism of phototoxicity. Overall, the data indicates that combining charge transfer and iodination is an effective strategy for enhancing phototherapeutic capacity of BODIPY PS.
在活的癌细胞系和非癌细胞系中比较了一系列硼二吡咯-苝电荷转移二元化合物的摄取和光毒性，以评估它们在成像和光动力疗法（PDT）中的性能。比较了化合物中位碘化和甲磺酰化对其光学性质、细胞摄取和毒性的影响。值得注意的是，在所有衍生物中，这些探针在高达50μM（测试的最大浓度）时暗毒性极小，但在纳摩尔IC值下表现出出色的光毒性和令人印象深刻的光毒性指数（PI，暗IC与光IC的比值），甲磺酰化碘化衍生物MB2PI表现最佳，在MCF-7细胞和肿瘤球体中的PI分别>218和>8.9。这显著高于MCF-7细胞中未碘化的类似物MB2P，其观察到的PI>109，略高于球体中PI>8的MB2PI。该化合物还显示出有趣的发射光谱变化，其定位对炎症刺激有反应。进一步的研究证实了硼二吡咯能有效产生单线态氧，表明其光毒性的II型机制。总体而言，数据表明结合电荷转移和碘化是增强硼二吡咯光动力治疗能力的有效策略。
