| In the past 20 years, nanotechnology has undergoed fast progress. Because the favorable physical and chemical properties and biocompatibility of mesoporous silica nanoparticles(MSNs), and they have been widely applied in drug delivery, drug targeting, gene transfection and cell tracking. Although the in vitro intensive studies of drug delivery systems(DDSs) based on functionalized mesoporous silica nanoparticles(MSNs) in the past decades have achieved many well-established results, in vivo evaluations of these systems concerning therapeutic efficiency and biosafety were started only in recent years.In this paper, we develope this research through the following steps:(1) Firstly, synthesis of MSNs-NH2 using sol–gel methods incorporated by APTES, Which exhibits a very uniform particle size distribution around 120?160 nm, a disordered porous structure and a perfect mono-dispersivity.(2) Secondly, conjugation of heparin that is a functional activity molecular with MSNs-NH2 and formation the heparinize mesoporous silica nanoparticles(MSNs-HP). The results show that the immobilization of heparin onto MSNs-NH2 has no effect on its morphology, but the BET surface area, pore volume, pore size and the zeta potential of MSNs-NH2 reduced from 552 cm2 g-1, 0.74 cm3 g-1, 2.58 nm and 34 mV to 329 cm2 g-1, 0.40 cm3 g-1, 2.07 nm, and ?43 mV respectively, and the immobilization efficiency of heparin was approximately 2%(w/w) as determined by toluidine blue assay.(3)Lastly, loading of DOX into heparinized MSNs by physical adsorption. 4%(w/w) of DOX loading capacity onto MSNs-HP was confirmed by UV?vis measurements at the wave-length of 480 nm. According to the release profile in vitro and vivo of DOX from MSNs-HP, it can be seen that after the burst release of DOX within the initial 8 h, the release process could be sustained to more than 70 h. When loaded MSNs-HP was intravenously administered, the initial peak concentration of DOX in plasma could be maintained up to 6 h. These results suggest that MSNs-HP is able to penetrate into cancer cells and delaying the release of anticancer drug doxorubicin(DOX) and thus could be helpful for improving therapeutic efficacy.In vivo evaluation on the animal xenograft models showed that MSNs–HP which loaded small amounts of drugs can be achieved similar results with large dose of antitumor drugs. The tumor inhibitory rate of loaded MSNs-HP(58%) was much more than that of DOX inside nanoparticles alone(18%) and close to that large(7-fold) doses of DOX(67%) alone, indicating that the use of MSNs-HP was able to significantly increase the antitumor efficacy of DOX. Furthermore, this system was found safer than large doses of drug. These factors might enable MSNs-HP to be a high-efficiency and low toxicity carrier for anticancer drug delivery. |
