Preparation, characterization, and in vitro evaluation of folate-modified mesoporous bioactive glass for targeted anticancer drug carriers

Abstract

Functionalized mesoporous bioactive glasses (MBGs) with folic acid (FA) were evaluated specifically for targeting cancer cells because of the high abundance of folate receptors (FRs) in numerous cancer cells. The folate-modified MBG (MBG-FA) was used as a targeted anticancer drug delivery carrier to investigate receptor-mediated targeting characteristics. At the same time, in vitro cytotoxicity and cell uptake of FA-grafted MBG (MBG-FA) to HeLa and L929 cell lines were evaluated. MBG-FA was nontoxic up to a concentration of 200 μg mL⁻¹, and can be specifically raised by HeLa and L929 cells through FA receptor-mediated endocytosis. In vitro cellular uptakes of MBG-FA were investigated with a fluorescence microscope, which demonstrates considerably higher internalization of the MBG-FA by HeLa epithelial carcinoma cells, which are overexpressed folate receptors (FRs), than the cellular uptake by L929 fibroblast cells, which are deficient folate receptors (FRs). Camptothecin (CPT), a water-insoluble anticancer drug, was delivered into cancer cells; surface conjugation with cancer-specific targeting agents increased the uptake into cancer cells relative to non-cancerous fibroblasts. CPT had a sustained release pattern from MBG-FA, and the CPT-loaded MBG-FA exhibited greater cytotoxicity than free CPT because of the increased cell uptake of anticancer drug delivery vehicles mediated by the FA receptor. The structural, morphological, and textural features were characterized well by X-ray diffraction (XRD), transmission electron microscopy (TEM), and N₂ adsorption/desorption. The results reveal that the MBG exhibited typical ordered characteristics of the hexagonal mesostructure. Therefore, this study concludes that the MBG-FA system demonstrates great potential in the targeted intelligent drug delivery systems (DDSs) and cancer-therapy fields.