In vitro breast cancer targeting using Trastuzumab-conjugated mesoporous silica nanoparticles: Towards the new strategy for decreasing size and high drug loading capacity for drug delivery purposes in MSN synthesis

Abstract

Abstract In the present study, an efficient protocol was introduced for synthesis of biocompatible mesoporous silica nanoparticles (MSN) with an adequate size and high drug loading capacity. Herein, the tri-ethanolamine, TEA, dominantly controlled the pH of solution in addition to regulate nanoparticle sizes via complexing with ortho silicate functional group. Furthermore, ammonium nitrate as a weak acid was used for micellar template extraction and the results were compared with a common salt such as sodium chloride. The obtained results of BET analysis showed ammonium nitrate led to creation of pore sizes with 3.2 nm and enhanced specific surface area with 563 m2/g which were higher than NaCl route. In the next step, the surfaces of MSNs were functionalized with particular compounds, (3- Aminopropyl) tri-ethoxysilane, APTES, applied for amine functionalization whereas 1-Ethyl-3-(3- dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide, EDC/NHS, as cross link agent was used for Trastuzumab modification of silica nanoparticles which were subsequently loaded with doxorubicin for studying the targeted breast cancer therapy. Moreover, fluorescein dye was optimized on the surface modified nanoparticles. The molecular fluorescence imaging was used to confirm the significant attachments of our surface modified MSNs to plasma membrane of breast cancer cell lines (HER2 overexpressed SKBR3 cell lines). Furthermore, drug loading capacity of the presented nano-carriers was calculated and shown to be 57.40% for doxorubicin suggesting its priority in the biological application comparing to other reported ones. Finally, quantum chemical study at B3lyp/6–311++g** level of theory was performed to reveal the pH-triggered release of doxorubicin loaded on these nanoparticles which the obtained results were in agreement with experimental evidences.