Abstract
Mesoporous silica has aroused lots of interest in biomedical fields, in which novel kinds of mesoporous silica with tunable mesoporosity and size have attracted much attention, but functionalization or multi-functionalization inside the mesopores of these structures is still rarely detected. Among all the functionalized molecules, beta cyclodextrin hydrate (β-CD), a kind of hydrophilic non-toxic carrier for hydrophobic drugs, can increase the solubility and bioavailability of drugs, acting as a pH responsive "gate" when functionalized on the surface of mesoporous silica. Herein, we functionalized β-CD inside novel kinds of mesoporous silica or magnetic mesoporous silica as the physical binding sites for the model drug curcumin through an out-inside two step bifunctionalization process including a vacuum pumping recrystallization drug loading process. According to the physical characterization with XRD, FT-IR, XPS, solid state NMR, BET, TG, DTA, TEM and DLS, the drug delivery nanosystems were successfully fabricated and contained nano-formulations of curcumin. In vitro cell testing, including Cell Counting Kit-8, Hoechst 33342 staining, hemolysis experiments and cell apoptosis, indicated that through the bifunctionalization, the biocompatibility of the mesoporous silica with cells could be improved, and the toxicity of the drug delivery nano-formulations towards two kinds of cancer cells, SK-HEP1 and HepG2, was significantly increased compared with free curcumin. In vitro release studies revealed that the nano-formulations contained more suspended curcumin molecules as described by the Higuchi models and showed enhanced pH responsive release properties, and that the magnetic nano-formulations exhibited alternating magnetically controlled release properties. The confocal microscopy analysis results revealed the obviously increasing intercellular release and uptake of both nano-formulations of curcumin by SK-HEP1 cells and the "on" and "off" stages of the alternating magnetism responsive intercellular release properties of the fabricated magnetic nano-formulations. The bifunctionalization process combined with the nanostar structure has immense potential in the drug delivery field, especially for hydrophobic drugs.
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