In vitroandin vivoevaluation of paclitaxel-loaded mesoporous silica nanoparticles with three pore sizes

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In the present study, mesoporous silica nanoparticles (MSNs) with three pore size were manufactured by the etch method. A typical chemotherapeutic agent, paclitaxel (PTX) was loaded into these MSNs. The in vitro drug release behavior, the in vitro anti-tumor activity, the morphological apoptosis cell changes, cell apoptosis rate and pharmacokinetics were extensively evaluated to clarify the biomedical roles of these MSNs in the application of drug delivery. The results showed that paclitaxel-loaded MSNs not only demonstrated effective drug loading but also exhibited pore-size-dependent drug release performance in vitro. In addition, MSNs exhibited pore-size-dependent anti-tumor activity against breast cancer MCF-7 cells. The apoptosis mechanism study demonstrated that the percentage of early and late apoptosis of all PTX-loaded MSNs treated MCF-7 cells were significantly higher than that of free PTX, and additionally the percentage of apoptosis for PTX-loaded MSNs increased as the pore size of carriers enlarged. The pharmacokinetics results showed that PTX-loaded MSNs with the largest pore size exhibited the pharmacokinetic property similar to the PTX solution and the other drug loaded MSNs displayed sustained release behavior. These results demonstrate that MSNs could be a very promising drug delivery system for pore-size controllable drug release and enhancing the anti-tumor activity.

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