Zahra Mehak, Abrahamse Heidi, George Blassan P
Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 1711, Doornfontein 2028, South Africa.
Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 1711, Doornfontein 2028, South Africa.
Biomed Pharmacother. 2025 Jul;188:118227. doi: 10.1016/j.biopha.2025.118227. Epub 2025 Jun 3.
Breast cancer remains a formidable health challenge despite significant advancements in treatment modalities. This study investigates the therapeutic potential of green-synthesized gold nanoparticles (AuNPs), utilizing Dicoma anomala methanolic leaf extract as a reducing and stabilizing agent, for targeted photodynamic therapy (PDT). The AuNPs were synthesized via a bottom-up approach and subsequently modified with liposomes (LIP) encapsulating the photosensitizer pheophorbide-a (PPBa), forming a nanocomplex (AuNPs-LIP-PPBa) through the thin-film hydration method. Comprehensive physicochemical characterization was conducted using UV-Vis spectroscopy, drug loading and release kinetics, Fourier-transform infrared spectroscopy (FT-IR), high-resolution transmission electron microscopy (HR-TEM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). The cytotoxic effects of AuNPs, PPBa, and the AuNPs-LIP-PPBa nanocomplex were evaluated against MDA-MB-231 triple-negative breast cancer cells using the MTT viability assay. The IC values were 0.30 µg/mL for PPBa, 92 µg/mL for AuNPs, and 10 µg/mL for the AuNPs-LIP-PPBa complex. Although PPBa alone showed higher cytotoxicity, the superior therapeutic efficacy of the AuNPs-LIP-PPBa complex in the context of PDT can be attributed to enhanced drug delivery, improved cellular uptake, and efficient activation of PPBa by the 660 nm laser, generating reactive oxygen species (ROS) and inducing cell death. This synergistic effect highlights the potential of the AuNPs-LIP-PPBa complex as an effective strategy for PDT-based cancer therapy. Additional mechanistic studies, including reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) assays, revealed enhanced apoptotic activity in treated cells. Triplicate experiments (n = 3) were conducted for each condition, with biological replicates used to ensure the reliability of the results. The data confirmed a significant reduction in cell viability, with the nanocomplex exhibiting superior therapeutic efficacy compared to individual treatments. Furthermore, this study explores the innovative integration of green-synthesized AuNPs with liposomal drug delivery systems and photosensitizers, presenting an eco-friendly strategy to improve PDT outcomes. The primary objective of this research is to assess the effectiveness of the AuNPs-LIP-PPBa nanocomplex in enhancing the delivery of the photosensitizer Pheophorbide-a for photodynamic therapy. The results provide strong support for further preclinical and clinical studies aimed at advancing nanotherapeutics for breast cancer treatment.
尽管治疗方式有了显著进步，但乳腺癌仍然是一个严峻的健康挑战。本研究利用异常地锦草甲醇叶提取物作为还原剂和稳定剂，研究绿色合成金纳米颗粒（AuNPs）在靶向光动力疗法（PDT）中的治疗潜力。通过自下而上的方法合成AuNPs，随后用包裹有光敏剂脱镁叶绿酸-a（PPBa）的脂质体（LIP）进行修饰，通过薄膜水化法形成纳米复合物（AuNPs-LIP-PPBa）。使用紫外可见光谱、药物负载和释放动力学、傅里叶变换红外光谱（FT-IR）、高分辨率透射电子显微镜（HR-TEM）、扫描电子显微镜（SEM）和能量色散X射线光谱（EDS）进行了全面的物理化学表征。使用MTT活力测定法评估了AuNPs、PPBa和AuNPs-LIP-PPBa纳米复合物对MDA-MB-231三阴性乳腺癌细胞的细胞毒性作用。PPBa的IC值为0.30μg/mL，AuNPs为92μg/mL，AuNPs-LIP-PPBa复合物为10μg/mL。虽然单独的PPBa显示出更高的细胞毒性，但在PDT背景下，AuNPs-LIP-PPBa复合物的卓越治疗效果可归因于增强的药物递送、改善的细胞摄取以及660nm激光对PPBa的有效激活，产生活性氧（ROS）并诱导细胞死亡。这种协同效应突出了AuNPs-LIP-PPBa复合物作为基于PDT的癌症治疗有效策略的潜力。包括活性氧（ROS）生成和线粒体膜电位（MMP）测定在内的额外机制研究揭示了处理后细胞中凋亡活性的增强。对每种情况进行了三次重复实验（n = 3），使用生物学重复以确保结果的可靠性。数据证实细胞活力显著降低，与单独治疗相比，纳米复合物表现出卓越的治疗效果。此外，本研究探索了绿色合成的AuNPs与脂质体药物递送系统和光敏剂的创新整合，提出了一种改善PDT结果的生态友好策略。本研究的主要目的是评估AuNPs-LIP-PPBa纳米复合物在增强光敏剂脱镁叶绿酸-a用于光动力疗法递送方面的有效性。这些结果为旨在推进乳腺癌治疗纳米疗法的进一步临床前和临床研究提供了有力支持。
