Nkune Nkune Williams, Abrahamse Heidi
Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein, P.O. Box 17011, Johannesburg 2028, South Africa.
Pharmaceutics. 2023 Aug 31;15(9):2264. doi: 10.3390/pharmaceutics15092264.
Melanoma remains a major public health concern that is highly resistant to standard therapeutic approaches. Photodynamic therapy (PDT) is an underutilised cancer therapy with an increased potency and negligible side effects, and it is non-invasive compared to traditional treatment modalities. Three-dimensional multicellular tumour spheroids (MCTS) closely resemble in vivo avascular tumour features, allowing for the more efficient and precise screening of novel anticancer agents with various treatment combinations. In this study, we utilised A375 human melanoma spheroids to screen the phototoxic effect of zinc phthalocyanine tetrasulfonate (ZnPcS) conjugated to gold nanoparticles (AuNP). The nanoconjugate was synthesised and characterised using ultraviolet-visible spectroscopy, a high-resolution transmission electron microscope (TEM), dynamic light scattering (DLS), and zeta potential (ZP). The phototoxicity of the nanoconjugate was tested on the A375 MCTS using PDT at a fluency of 10 J/cm. After 24 h, the cellular responses were evaluated via microscopy, an MTT viability assay, an ATP luminescence assay, and cell death induction using annexin propidium iodide. The MTT viability assay demonstrated that the photoactivated ZnPcS, at a concentration of 12.73 µM, caused an approximately 50% reduction in the cell viability of the spheroids. When conjugated to AuNPs, the latter significantly increased the cellular uptake and cytotoxicity in the melanoma spheroids via the induction of apoptosis. This novel Zinc Phthalocyanine Nanoconjugate shows promise as a more effective PDT treatment modality.
黑色素瘤仍然是一个重大的公共卫生问题,对标准治疗方法具有高度抗性。光动力疗法(PDT)是一种未得到充分利用的癌症治疗方法,其效力增强且副作用可忽略不计,与传统治疗方式相比,它是非侵入性的。三维多细胞肿瘤球体(MCTS)与体内无血管肿瘤特征非常相似,能够更高效、精确地筛选具有各种治疗组合的新型抗癌药物。在本研究中,我们利用A375人黑色素瘤球体来筛选与金纳米颗粒(AuNP)偶联的四磺酸酞菁锌(ZnPcS)的光毒性作用。使用紫外可见光谱、高分辨率透射电子显微镜(TEM)、动态光散射(DLS)和zeta电位(ZP)对该纳米偶联物进行合成和表征。使用PDT在10 J/cm的光通量下对A375 MCTS测试该纳米偶联物的光毒性。24小时后,通过显微镜检查、MTT活力测定、ATP发光测定以及使用膜联蛋白碘化丙啶诱导细胞死亡来评估细胞反应。MTT活力测定表明,浓度为12.73 μM的光活化ZnPcS使球体的细胞活力降低了约50%。当与AuNP偶联时,后者通过诱导细胞凋亡显著增加了黑色素瘤球体中的细胞摄取和细胞毒性。这种新型酞菁锌纳米偶联物有望成为一种更有效的PDT治疗方式。