Benzo[a]phenoselenazine-based NIR photodynamic therapy for the treatment of COX-2 overexpressing cancer cells.

IF 3.2 4区医学 Q3 CHEMISTRY, MEDICINAL

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-02-14 DOI:10.1080/17568919.2025.2463878

Kalayou Hiluf Gebremedhin

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引用次数: 0

Abstract

Background: Upregulation of Cyclooxygenase-2 (COX-2) in a variety of cancer cell lines, a key enzyme of prostaglandin biosynthesis, relative to surrounding normal tissues results in the use of the COX-2 protein as an attractive molecular target for many anticancer therapeutics. This could have a significant implication for selective destruction of cancer cells via the photodynamic therapy effects, leaving the normal tissue intact.

Experimental: Here, a COX-2-specific NIR photosensitizer (Se-C₆-IMC) was synthesized and developed by conjugating a classic anti-inflammatory drug indomethacin (IMC) as an efficient recognition group for COX-2 protein, with benzo[a]phenoselenazine derivative photosensitizer through hexanediamine linker.

Result and discussion: In this study, Se-C₆-IMC exhibited a strong NIR absorption in the phototherapeutic window, relatively high ¹O₂ generation (Φ_Δ = 0.74 in CH₂C₂), and an excellent phototoxicity (IC₅₀ = 0.04 µM, 14.4 J/cm²) against MCF-7 cells as compared to COS-7 cells lacking COX-2 protein expression.

Conclusion: Se-C₆-IMC showed the highest intracellular localization in Golgi apparatus, making it to more effective for cellular destruction and Golgi targeted therapy. Thus, Se-C₆-IMC might hold great promise as a COX-2-specific NIR photosensitizer for improving the PDT efficiency and new Golgi-targeted PDT development in the future.

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苯并[a]基于吩硒化嗪的近红外光动力疗法治疗COX-2过表达癌细胞。

背景：环氧化酶-2 （COX-2）在多种癌细胞系中的上调，是前列腺素生物合成的关键酶，相对于周围正常组织，导致COX-2蛋白被用作许多抗癌治疗的有吸引力的分子靶点。这可能对通过光动力治疗作用选择性破坏癌细胞，使正常组织完好无损具有重要意义。实验：将经典抗炎药吲哚美辛（IMC）作为COX-2蛋白的有效识别基团，通过己二胺连接剂与苯并[a]吩硒化嗪衍生物光敏剂偶联，合成了COX-2特异性近红外光敏剂Se-C6-IMC。结果和讨论：与缺乏COX-2蛋白表达的COS-7细胞相比，Se-C6-IMC在光治疗窗口表现出较强的近红外吸收，相对较高的10o2生成（ΦΔ = 0.74 CH2C2），对MCF-7细胞具有优异的光毒性（IC50 = 0.04µM, 14.4 J/cm2）。结论：Se-C6-IMC在高尔基体中具有较高的胞内定位，具有较好的细胞破坏和高尔基体靶向治疗效果。因此，Se-C6-IMC作为cox -2特异性近红外光敏剂，在提高PDT效率和新型高尔基PDT开发方面具有很大的前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Future medicinal chemistry CHEMISTRY, MEDICINAL-

CiteScore

5.80

自引率

2.40%

发文量

118

审稿时长

4-8 weeks

期刊介绍： Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.