Targeted photodynamic therapy for MCF-7 breast cancer using antibody-conjugated, green-synthesized gold nanoparticles loaded with hypericin: a proof of concept

The treatment of breast cancer remains a significant clinical challenge, with limited responsiveness to conventional therapies. Photodynamic therapy, using the natural photosensitizer Hypericin, offers a promising modality, but its efficacy is limited by poor solubility, poor selectivity, and non-specific binding. To address these limitations, we developed a targeted nanoplatform leveraging the biocompatibility of gold nanoparticles and targeting capabilities of a monoclonal antibody. This study aimed to synthesize and characterize a novel nanoplatform comprising eco-friendly, green-synthesized gold nanoparticles, loaded with Hypericin, and conjugated with a monoclonal antibody for the targeted photodynamic therapy for MCF-7 breast cancer cells. Gold nanoparticles were synthesized using a green-chemistry approach with an aqueous extract of Kniphophia porphyrantha. Hypericin was loaded onto the nanoparticle surface, followed by the monoclonal antibody attachment to create the bionanoconjugate. The conjugate was characterized by UV-Vis spectroscopy, DLS, and TEM. Cellular uptake and phototoxicity of the nanoplatform were evaluated in MCF-7 cells and compared to non-targeted controls using microscopy, MTT and LDH assay, and flow cytometry upon irradiation with 594 nm diode laser. Treatment with free Hypericin resulted in a 50% reduction in cell viability, while the bionanoconjugate displayed pronounced cytotoxic effects with less than 30% of the cell population remaining viable. 70% reduction in ATP levels was observed in cells treated with the bionanoconjugate, in comparison to only 20% in cells treated with free Hypericin. These results demonstrate the enhanced PDT efficacy resulting from nanoparticle-antibody conjugation.