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

Xiaohui Wu, Zheng Han, Rebecca M. Schur, Zheng Rong Lu

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)501-507
Number of pages7
JournalACS Biomaterials Science and Engineering
Volume2
Issue number4
DOIs
StatePublished - Apr 11 2016
Externally publishedYes

Keywords

  • arsenic trioxide
  • breast cancer
  • nanoparticles
  • targeting

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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