TY - JOUR
T1 - Targeted Mesoporous Silica Nanoparticles Delivering Arsenic Trioxide with Environment Sensitive Drug Release for Effective Treatment of Triple Negative Breast Cancer
AU - Wu, Xiaohui
AU - Han, Zheng
AU - Schur, Rebecca M.
AU - Lu, Zheng Rong
PY - 2016/4/11
Y1 - 2016/4/11
N2 - 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.
AB - 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.
KW - arsenic trioxide
KW - breast cancer
KW - nanoparticles
KW - targeting
UR - http://www.scopus.com/inward/record.url?scp=84969277665&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84969277665&partnerID=8YFLogxK
U2 - 10.1021/acsbiomaterials.5b00398
DO - 10.1021/acsbiomaterials.5b00398
M3 - Article
AN - SCOPUS:84969277665
SN - 2373-9878
VL - 2
SP - 501
EP - 507
JO - ACS Biomaterials Science and Engineering
JF - ACS Biomaterials Science and Engineering
IS - 4
ER -