Research On Anti-cancer Drug Control Release Based On Mesoporous Nanopaticles

In this thesis, a special attention was paid to the application of mesoporous materials in anti-cancer drug control release fields.We successfully synthesized functionalized mesoporous silica nanoparticles (MSNs) and investigated its applications for sustained release of anti-cancer drugs (such as cisplatin,doxorubicin) and targeting treatment of liver cancer. Besides, we first successfully synthesized mesoporous carbon nanoparticles via a hydrothermal synthesis combined with hard template method. We employed these well dispersed and uniform MCNs as drug loading carries for CPT which is a representative hydrophobic chemotherapeutic drug and discussed the loading and sustained release properties of this system.High-density carboxyl group modified mesoporous nanoparticles with uniform particle size, large pore volume and high surface areas were successfully synthesized. Carboxyl groups were served to bind cisplatin which is a widely used antitumor drug. The loading amount, release property and antitumor activity against MCF-7 and HeLa cells were reviewed here. Due to those strong interactions between drug and MSNs together with amazing adsorption property of this material, extraordinarily high drug loading efficiency up to 95% in MSNs was achieved and the loaded CDDP showed a greatly sustained release in PBS buffer for as long as 13 days. It is interestingly noted that drug release is acid dependent and CDDP@MSNs had a higher antitumor efficiency than the free CDDP against both MCF-7 and HeLa cell lines.Mesoporous nanoparticles were simultaneously modified with polyethylene glycol and galactose for liver cancer targeting and anticancer drug delivery. Anticancer drug, doxorubicin (Dox) was effectively loaded into nanoparticles at a large content (906mg/g) with high efficiency (90.6%). The drug delivery system could be actively targeted to the liver cancer cells due to the special recognization of the modified galatose on their outer surface by the overexpressed ASGP receptor in HepG2 cell surface. Therefore, the resultant nanocarriers were effectively directed to the target cancer cells and inhibited the growth of HepG2 cells more effectively that that of free drugs and unmodified nanocarrers.Uniform MCNs with size below 200 nm and good water dispersibility were successfully prepared, which is the negative replica of the parent MCM-48 type MSNs. Amino group modification for the blank MSNs is decisive step for the infiltration of the carbon resource precursors for hydrothermal treatment into the pore channels of the nanoparticle template. Typical anticancer drug of CPT was exemplified to load inside the obtained MCNs and the loading capacity was very high. A prolonged release profile for CPT from MCNs over 5 days was present. Thus, it is expected that the present method will lead to further development of fabrication of favorable porous carbon materials for biomedical applications.