Targeted Mesoporous Silica Nanoparticles Delivering Arsenic Trioxide with Environment Sensitive Drug Release for Effective Treatment of Triple Negative Breast Cancer.

Abstract

In this study, we report a novel modality of using a mesoporous silica nanoparticles (MSNs)-based drug delivery system with RGD peptide as a targeting ligand to load arsenic trioxide (ATO) (ATO-MSNs-RGD) for treating MDA-MB-231 triple-negative breast cancer. The MSNs, ATO-MSNs, and ATO-MSNs-RGD were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), transmission electron microscopy (TEM), and Brunauer-Emmet-Teller (BET) method. The data indicated that the MSNs possessed MCM-41 type mesopores with high surface area of ∼1021 m2/g and pore diameter of ∼2.2 nm. However, both values dramatically decreased after MSNs were encapsulated with ATO or modified with RGD. The amount of surface anchored RGD peptide was determined to be 0.20 mmol/g. Glutathione (GSH) greatly enhanced ATO release from MSNs. Confocal laser microscopy images demonstrated that both ATO-MSNs and ATO-MSNs-RGD had good cellular uptake that improved with longer incubation time and nanoparticle concentration and the ATO-MSNs-RGD showed clearly improved cellular uptake compared with ATO-MSNs. The MSNs, ATO-MSNs, ATO-MSNs-RGD, and ATO were used to treat mice bearing MDA-MB-231 breast tumors every 5 days and the findings suggested that ATO-MSNs-RGD provided superior therapeutic ability over MSNs, ATO-MSNs, and ATO.