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八羧基酞菁镓(Ⅲ)羟基化物作为一种潜在的促凋亡药物治疗皮肤癌细胞。

Gallium octacarboxyphthalocyanine hydroxide as a potential pro-apoptotic drug against cancer skin cells.

机构信息

Faculty of Chemistry, University of Opole, Oleska 48, Opole 45-052, Poland.

Faculty of Chemistry, University of Opole, Oleska 48, Opole 45-052, Poland.

出版信息

Bioorg Chem. 2024 Nov;152:107736. doi: 10.1016/j.bioorg.2024.107736. Epub 2024 Aug 28.

DOI:10.1016/j.bioorg.2024.107736
PMID:39208675
Abstract

Novel anticancer strategies reduce side effects on healthy tissues by elevating the lethal abilities of cancer cells. The development of effective particles with good bioavailability and selectivity remains problematic. For undesirable features, green chemistry is used to synthesize the best compounds, or natural-based particles are improved. Photodynamic therapy (PDT), modelled on phthalocyanines (Pcs), still delivers second-generation sensitizers which are complemented with metal ions, such as Zn, Al, or Ga. Gallium octacarboxyphthalocyanine hydroxide (Ga(OH)PcOC), was designed for skin cancer treatment, and was used as a pro-apoptotic and pro-oxidative agent on normal skin cell lines, fibroblasts (NHDF), and keratinocytes (HaCaT), with promising selectivity against melanoma cancer cells (Me45) in vitro. Compared to the previous reported findings, where the ZnPcOC acted on the skin cell lines at higher doses, the sensitivities to the Ga(OH)PcOC allows for an effective reduction of the sensitizer dose. The effective dose, for a novel Ga(OH)PcOC particle, was significantly reduced from 30 µM to 6 µM on Me45 cancer cells, tested using 24 h MTT viability, as well as cytometric pro-oxidative and pro-apoptotic assays. The promising photosensitizer did not reduce viability in normal fibroblasts and keratinocytes without reactive oxygen species (ROS) elevation or apoptosis induction. The improvement to the previous findings is better Ga-based photosensitizer selectivity against the cancer Me45 cells, then observed in Zn-based compounds.

摘要

新型抗癌策略通过提高癌细胞的致死能力来减少对健康组织的副作用。具有良好生物利用度和选择性的有效粒子的开发仍然存在问题。对于不理想的特性,绿色化学被用于合成最佳化合物,或改进基于天然的粒子。基于酞菁(Pcs)的光动力疗法(PDT)仍在使用第二代增敏剂,这些增敏剂辅以金属离子,如 Zn、Al 或 Ga。八羧基酞菁化镓氢氧化物(Ga(OH)PcOC)被设计用于治疗皮肤癌,并被用作正常皮肤细胞系成纤维细胞(NHDF)和角质细胞(HaCaT)的促凋亡和促氧化剂,对体外黑素瘤癌细胞(Me45)具有良好的选择性。与之前报道的研究结果相比,ZnPcOC 在较高剂量作用于皮肤细胞系,Ga(OH)PcOC 的敏感性允许有效降低增敏剂剂量。在用 24 小时 MTT 活力以及细胞计量促氧化和促凋亡测定法测试时,新型 Ga(OH)PcOC 颗粒的有效剂量从 30 µM 显著降低至 6 µM,作用于 Me45 癌细胞。这种有前途的光敏剂在不增加活性氧物种(ROS)或诱导细胞凋亡的情况下,不会降低正常成纤维细胞和角质细胞的活力。与基于 Zn 的化合物相比,对先前研究结果的改进是针对癌症 Me45 细胞的基于 Ga 的光敏剂选择性更好。

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