A berberine-functionalized green silver nanoplatform for combined chemo-photodynamic therapy against breast cancer cells.

Abstract

Breast cancer remains a leading cause of cancer-related mortality among women, while recurrence, multidrug resistance, and systemic toxicity continue to limit therapeutic outcomes. Berberine (BBR), a natural isoquinoline alkaloid with chemo-photodynamic potential, exhibits promising anticancer activity; however, poor solubility, low cellular uptake, and rapid photodegradation restrict its clinical application. This study developed and evaluated berberine-loaded biogenic silver nanoparticles (BBR-AgNPs) as a multifunctional nanoplatform for enhanced breast cancer therapy. BBR-AgNPs were synthesized using Senna didymobotrya leaf extract and characterised using UV-vis, fluorescence spectroscopy, FTIR, DLS, zeta potential analysis, SEM-EDS, and HR-TEM. Photochemical activity was assessed by generating singlet oxygen and reactive oxygen species (ROS) under 405 and 470 nm irradiation, while biological activity was evaluated in MCF-7 and MDA-MB-231 breast cancer cells. The nanoparticles exhibited a negative surface charge (-32.6 mV) and a hydrodynamic diameter of approximately 300 nm, with size heterogeneity evident from DLS analysis. BBR-AgNPs generated significantly higher ROS levels and enhanced photocytotoxicity compared with free BBR, reducing IC₅₀ values below 2.0 µg mL^-1 in MCF-7 cells and to approximately 3.0 µg mL^-1 in MDA-MB-231 cells under irradiation. Nanoparticle delivery also enhanced intracellular BBR uptake, mitochondrial depolarization, and apoptosis, supporting the potential of BBR-AgNPs as a combined chemo-photodynamic platform for further investigation in breast cancer models.