Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Johannesburg 2028, South Africa.
Int J Mol Sci. 2023 Jan 18;24(3):1902. doi: 10.3390/ijms24031902.
This work reports for the first time on the synthesis, characterization, and photodynamic therapy efficacy of the novel aluminium (III) chloride 2(3), 9(10), 16(17), 23(24)-tetrakis-(sodium 2-mercaptoacetate) phthalocyanine (AlClPcTS41) when alone and when conjugated to PEGylated copper-gold bimetallic nanoparticles (PEG-CuAuNPs) as photosensitizers on colon cancer cells (Caco-2). The novel AlClPcTS41 was covalently linked to the PEG-CuAuNPs via an amide bond to form AlClPcTS41-PEG-CuAuNPs. The amide bond was successfully confirmed using FTIR while the crystal structures were studied using XRD. The morphological and size variations of the PEG-CuAuNPs and AlClPcTS41-PEG-CuAuNPs were studied using TEM, while the hydrodynamic sizes and polydispersity of the particles were confirmed using DLS. The ground state electron absorption spectra were also studied and confirmed the typical absorption of metallated phthalocyanines and their nanoparticle conjugates. Subsequently, the subcellular uptake, cellular proliferation, and PDT anti-tumor effect of AlClPcTS41, PEG-CuAuNPs, and AlClPcTS41-PEG-CuAuNPs were investigated within in vitro Caco-2 cells. The designed AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs demonstrated significant ROS generation abilities that led to the PDT effect with a significantly decreased viable cell population after PDT treatment. These results demonstrate that the novel AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs had remarkable PDT effects against Caco-2 cells and may trigger apoptosis cell death pathway, indicating the potential of the AlClPcTS41 and AlClPcTS41-PEG-CuAuNPs in enhancing the cytotoxic effect of PDT treatment.
这项工作首次报道了新型铝（III）氯化物 2(3)、9(10)、16(17)、23(24)-四-(2-巯基乙酸钠)酞菁（AlClPcTS41）的合成、表征和光动力治疗效果，当其单独使用和与聚乙二醇化铜金双金属纳米粒子（PEG-CuAuNPs）缀合作为光敏剂用于结肠癌细胞（Caco-2）时。新型 AlClPcTS41 通过酰胺键共价连接到 PEG-CuAuNPs 上，形成 AlClPcTS41-PEG-CuAuNPs。酰胺键通过傅里叶变换红外光谱（FTIR）成功确认，而晶体结构则通过 X 射线衍射（XRD）进行研究。使用 TEM 研究了 PEG-CuAuNPs 和 AlClPcTS41-PEG-CuAuNPs 的形态和尺寸变化，使用 DLS 确认了颗粒的水动力尺寸和多分散性。还研究了基态电子吸收光谱，并确认了金属化酞菁及其纳米粒子缀合物的典型吸收。随后，在体外 Caco-2 细胞中研究了 AlClPcTS41、PEG-CuAuNPs 和 AlClPcTS41-PEG-CuAuNPs 的亚细胞摄取、细胞增殖和光动力治疗抗肿瘤作用。设计的 AlClPcTS41 和 AlClPcTS41-PEG-CuAuNPs 表现出显著的 ROS 生成能力，导致 PDT 治疗后活细胞群体明显减少。这些结果表明，新型 AlClPcTS41 和 AlClPcTS41-PEG-CuAuNPs 对 Caco-2 细胞具有显著的 PDT 作用，并可能触发细胞凋亡死亡途径，表明 AlClPcTS41 和 AlClPcTS41-PEG-CuAuNPs 具有增强 PDT 治疗细胞毒性作用的潜力。
