Novel chemo-photothermal therapy in breast cancer using methotrexate loaded folic acid conjugated Au@SiO2 nanoparticles

Abstract

Absolutely breast cancer patients need novel combined therapies with effective function and fewer side effects. Low level laser therapy (LLLT) is known as safe type of phototherapy to target tumoric tissue/cells. Besides, using targeted nanoparticles increases the successfulness of cancer therapy. This study was designed for investigating the effect of combined folate (FA)/Methotrexate (MTX) loaded Au@SiO2 nanoparticles (NPs) and LLLT on fight against breast cancer. NPs were synthesized and characterized using FTIR, TEM and DLS-Zeta. After loading of MTX and FA on NPs, their cellular uptake and cytotoxic effects were evaluated in the presence of LLLT on breast cancer cells: MDA-MB231- and MCF-7. The NPs had spherical morphology with mean diameter of around 25nm and positive charge (13.3+ mV) while after conjugation with FA and MTX their net charge reduced to around 19.7- mV. Our findings in cell uptake studies clearly showed enhanced cellular uptake of NPs after FA and MTX loaded NPs in both breast cancer cell lines especially on MDA-MB231- due to high expression of folate receptors. The results indicated that LLLT had proliferative effect on both breast cancer cell lines but in the presence of engineered breast cancer targeted nanoparticle, the efficacy of combination chemo-photothermal therapy were significantly increased using MTT assay (p<0.05), DAPI staining, and cell cycle findings. The highest apoptotic effect on breast cancer cell lines was observed in the cells exposed to combination of MTX-FA loaded Au@SiO2 NP and LLLT proved by DAPI staining and cell cycle(by increasing the cell arrest in subG0/G1). Taken together using a combination of nano-bio-chemotherapy and LLLT improves the potential of breast cancer therapy with minimum side effects.