| Cancer is one of most concerned diseases in the world, in which, there is still no reported specific targeted drugs with high effect. Mesoporous silica, with its superior biocompatibility properties, functionalizable surface and inner mesoporous channels, and easy adjustable mesoporous structure and particle's structures, is an inevitable candidate for fabricating smart targeted materials. Recently, there are some reported anti-cancer drugs,among them, curcumin, a kind of drug with range resources, has attracted large attentions among the researchers world wide with its bioactivity, i.e., anti-cancer, anti-inflammation,anti-oxidation and etc, but low water solubility and bioavalibility with unstable molecular structure,becoming the barrier to apply in in anti-cancer and leaving much more to be desired. Meanwhile, doxorubicin is a kind of traditional anti-cancer drug with good cancer cells' terminated properties and high stable molecular structure, has become one of the hottest choice to be studied as the mode drug by the global researchers with their developed diverse drug delivery systems. In addition, traditional mesoporous silica, with its small mesoporous channels, could not satisfy the needs of increasing drug loading capacity and loading specific nano metal and nano metallic oxide.According to those circumstances, we combined the soft-templating and electrostatic fabrication process and have success in fabrication large mesoporous silica loading magnetic particles, in which the samples were named as nanostar. Then, we used the out-inside fucntionalization process to modified the nanostar with thiol groups in the surface and beta-CD molecules inside mesoporous channels, meanwhile the curcumin molecules were loading inside the mesoporous channels according to the physical combination with the modified beta-CD molecules, therefore, the smart controlled drug delivery system was successfully fabricated. Through the characterizations, i.e., FTIR,XRD, XPS, BET and solid NMR, on the functionalized materials and drug delivery systems, we got the mechanism of mixed modification and drug loading process of large-mesoporous silica. Meanwhile, the structure and dispersion properties were investigated by TEM and DLS in detail. In addition, after the evaluation by cell experiments, we found the mixed functionalized materials had increased the biocompatiblity and lowered the cytotoxicity. When fabricating as the drug delivery systems, they had increased cytotoxicity, cellular uptake and release rate in acid media compared with pure curcumin. Meanwhile, the magnetic drug delivery systems are high sensitive to magnetic fields, from which the “on-off” smart controlled release could perform both in vitro release media and intracellular media.Afterwords, we tun the smart small molecule ammonia as the TEA for the mineralization condition, still, combining the soft templating and electrostatic fabricated process and out-inside mixed fucntioalized process, we gained the functionalized samples step wise, in which we further loaded them with nano Au and gain the Au loaded bi-functionalized samples. These materials we gained have high efficiency in Dox's loading.In addition, through the cell assay experiments, we gained the Au loaded an Au-Fe3O4 loaded materials with higher biocompatibility, while the Dox loading samples maintain the effect of killing cancer cells of Dox. Through the Au-Fe3O4 loading, the materials have increase in NMR diagnosis signal and responsive to p H, alternative magnetic field and near infrared lights by performing the smart “on-off” controlled release properties.Large-mesoporous silica, combination with the electrostatic self-assemble process and mixed functionalized process and nano Au composite, could be designed as loading materials for different drugs with higher NMR signals in diagnosis and sensitively responsive to different different external interference conditions. These findings will have immense future and inevitable value in biomaterials and drug controlled release fields. |
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