Metformin-loaded chitosan nanoparticles augment silver nanoparticle-induced radiosensitization in breast cancer cells during radiation therapy

Recent research has focused on enhancing tumor response to radiation therapy using radiosensitizers to increase radiation absorption by cancerous tissues. This study utilized silver nanoparticles (AgNPs) as radiation sensitizers and chitosan as a nanocarrier to deliver metformin to breast cancer cells. Metformin-loaded chitosan nano-particles (Met NPs) and AgNPs were synthesized and characterized. MCF-7 breast cancer cells were pretreated with Met NPs, followed by treatment with AgNPs and irradiation with X-rays at 2, 4, and 8 Gy doses. Cellular cytotoxicity, apoptosis, DNA damage, and 3D spheroid formation were evaluated. The synthesized Met NPs and AgNPs had average diameters of 51.5 +/- 9.4 nm and 3.02 +/- 0.03 nm, respectively. Cellular cytotoxicity assessment revealed the highest cytotoxicity in MCF-7 cells pretreated with Met NPs, treated with AgNPs, and irradiated with 8 Gy. Flow cytometry analysis demonstrated a 67.58 % apoptosis rate in cells pretreated with Met NPs, compared to 30.42 % in cells pretreated with plain metformin. DAPI staining revealed a 1.8-fold increase in DNA damage in cells pretreated with Met NPs and Ag NPs upon exposure to radiation. The 3D spheroid culture model confirmed a 60 % enhancement in the radiosensitivity of breast cancer cells in the presence of Met NPs and Ag NPs. The combination of Met NPs and Ag NPs represents a promising strategy to improve the therapeutic efficacy of radiation therapy for breast cancer treatment. The delivery of metformin can potentiate the radio-sensitizing effects of Ag NPs, offering a novel approach to enhance cancer cells' response to radiation.