The Effects Of Potassium Sodium Niobate Piezoelectric Materials On The Proliferation,Migration And Invasion Of Breast Cancer Cells And The Possible Mechanisms

Breast cancer has become the most commonly diagnosed cancer in the world and the most common cause of death among female cancer patients.For breast cancer patients,metastasis is the most difficult and dangerous stage in the occurrence and evolution of malignant tumors,and it also accounts for more than 90% breast cancer patients to die from solid tumors.Inhibition of breast cancer motility and effective anti-breast cancer methods will greatly alleviate breast cancer burden.Hence,based on the importance of the regulatory effects of material surface potentials on cell behaviors and the limitations of electric stimulation for tumor therapy,potassium sodium niobate(KNN)piezoceramics with stable and adjustable surface charges were used to study the effects of surface potentials on the migration and invasion behaviors of breast cancer and their mechanisms.The effects and mechanisms of polarized KNN nanoparticles with ultrasound(US)generating wireless,controllable electric stimulation on breast cancer cell viability were also studied.The main research contents and conclusions are as follows:1.KNN surface potentials could affect breast cancer cell motility and cytoskeleton.Taking advantage of the excellent ferroelectric properties of KNN piezoceramics,KNN samples with different surface potentials but the samiliar surface morphologies,compositions,and chemical structures were obtained by controllable polarization methods,and they were applied as model materials to investigate the effects of charges on breast cancer cell movements.It was found that compared with unpolarized KNN samples,polarized KNN samples with higher surface potentials had the tendency to promote normal cell movements and inhibit cancer cell movements.The polarized one with a piezoelectric constant of 80 p C/N could significantly inhibit the migration and invasion of breast cancer cells.Further,immunofluorescence staining and real-time quantitative polymerase chain reaction(PCR)showed that the possible reasons were the inhibition of breast cancer cell polarization,change of microtubule aggregation state,the formation of flat cell morphology and strong adhesion.2.Breast cancer cells subjected to polarized KNN piezoelectric nanoparticles stimulated by US could well inhibit cancer cell viability.Polarized KNN nanoparticles with good piezoelectric properties were used to co-culture with BMSC at different concentrations,and400 ?g/m L polarized KNN with good biocompatibility to BMSC was selected for further experiments.The breast cancer cells were treated with US and polarized KNN particles to detect cell viability,conduct cell dead and alive stain and morphological observation.The results indicated that when the two acted together for 24 h,the cell viability of highly metastatic,triple negative breast cancer(NTBC)MDA-MB-231 reduced to 30%;non-NTBC MCF-7 reduced to 35% and the cytoskeletal structures were completely destroyed;the movement abilities were completely lost.The experiments also showed that breast cancer cells subjected to the polarized KNN nanoparticles and US could cause redox imbalance,excessive reactive oxygen species(ROS)and promote cancer cells apoptosis.