Mucin-1 aptamer directed targeted delivery of Doxorubicin using mesoporous silica magnetic nanoparticles

Abstract

Doxorubicin has been established as the first-line chemotherapeutic agent for advanced metastatic breast cancer. However, the cardiotoxicity of doxorubicin is a significant limiting factor in its application. Aims The purpose of this study was to synthesize mesoporous silica magnetic nanoparticles that were conjugated to mucin1 (MUC-1) aptamer for targeted delivery of DOX to MUC-1 positive breast cancer cells. Materials and methods Magnetic nanoparticles were synthesized using thermal decomposition method and the final product was coated with mesoporous silica using Cetyl trimethyl ammonium bromide (CTAB), Tetraethyl orthosilicate (TEOS) and 3-Aminopropyl triethoxysilane (APTS). DOX was loaded in silica pores. Next, FITC and MUC-1 were conjugated. The physicochemical characteristics and structure of nanoparticles were assessed by FT-IR, TEM and DLS. Cytotoxicity of nanoparticles on MCF-7 and MDA-MB-231 cell lines was determined using MTT method. Finally, the uptake of nanoparticles was evaluated by Flow cytometry. Results Spherical and uniform DOX-loaded-mesoporous silica core shell magnetic nanoparticles were synthesized. Nanoparticles were stable in PBS and there was a significant difference between the amount of released drug at the pH of 7.4 and 6.4. Results of MTT assay suggested that DOX-SPION@SiO2-MUC-1, showed more toxicity in MCF-7 than MDA-MB-231 cell line. The uptake of DOX- SPION@SiO2-MUC-1 NPs in MCF-7 cells is significantly greater than its uptake in MDA-MB-231 cells. Discussion DOX loaded-mesoporous silica core shell magnetic nanoparticles were uniform, spherical and their size was about 26nm.Nanoparticles were stable in PBS while releasing DOX. The conjugation of mucin1 aptamer led to more toxicity of DOX in MCF-7 cell line than free DOX. Also, the uptake of MUC-1-conjugated nanoparticles was considerably increased in mucin1 positive cell line. These results suggest that DOX-SPION@SiO2-MUC-1 nanoparticles could be a potential targeting agent at the cellular level.