Mannoside-Functionalized Silica Nanocomposite-Encapsulated Doxorubicin for MDA-MB-231 Cancer Cell Targeting and Delivery
Yu‐Han Su, Han-Chen Lin, Hsing-Yen Li, Chih-Hsuan Lien, Yao‐Hsiang Shih, Chian‐Hui Lai
Abstract
The purpose of this study was to develop a carbohydrate silica nanocomposite, M-mDOX@SiO 2, that can specifically target cancer cells and release the drug doxorubicin (DOX) specifically in an acidic tumor microenvironment (TME). First, DOX@SiO 2 was prepared using the Stöber method to encapsulate DOX within silica nanoparticles (NPs). DOX@SiO 2 was then immersed in acidic PBS (pH 5) to obtain mesoporous silica-based NPs, termed mDOX@SiO 2 . Through mannoside and galactoside surface silane modification of mDOX@SiO 2, we obtained M-mDOX@SiO 2 (specifically targeting the MDA-MB-231 cell surface receptor) and G-mDOX@SiO 2 (a nontargeting control), respectively. The synthesized silica NPs were characterized through ultraviolet–visible (UV–vis) spectrophotometry, fluorescence spectrometry, dynamic light scattering, and transmission electron microscopy. The anthrone–sulfuric acid method was used to measure the NP surface sugar content, and thermogravimetric analysis was applied to estimate the content of DOX loaded inside the NPs. The drug release profiles of M-mDOX@SiO 2 in different pH buffer solutions demonstrated that M-mDOX@SiO 2 can effectively release DOX in an environment with a pH of 5; moreover, the drug release rate increased as pH decreased. Fluorescence spectrometry and confocal microscopy were used to image MDA-MB-231 cells specifically targeted by M-mDOX@SiO 2 . The MTT assay results revealed that M-mDOX@SiO 2 resulted in efficient cell growth inhibition. Finally, our animal experiments revealed that M-mDOX@SiO 2 demonstrated high antitumor efficacy. In conclusion, M-mDOX@SiO 2 has great potential as a drug delivery carrier.