Green synthesis of gold nanoparticles from Dicoma anomala extract coated with liposome-encapsulated pheophorbide-a for enhanced photodynamic therapy against MDA-MB-231 triple negative breast cancer cells

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 IC₅₀ 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.