Rational design of curcumin loaded multifunctional mesoporous silica nanoparticles to enhance the cytotoxicity for targeted and controlled drug release.

Curcumin has attracted increasing attentions in recent years due to its promising anticancer activities. However, the hydrophobicity of curcumin has limited greatly its efficacy in clinical trials. In this study, folate (FA)-receptor targeting mesoporous silica nanoparticles that promise high loadings of curcumin via pH-sensitive Schiff base reactions were constructed and examined for targeted delivery of curcumin. Such nano-delivery system showed significantly improved stability and biocompatibility of curcumin under physiological conditions. Further investigations demonstrated that this nanocarrier had high values of drug loading efficiency (9.5%) and pH-responsive drug release property. Moreover, the particles could be efficiently internalized by FA-receptor-rich MCF-7 cells through the receptor-mediated endocytosis, whereas FA-receptor-poor HEK-293T normal cells showed much lower endocytosis of the nanoparticles under the same conditions. The in vitro cytotoxicity assay indicated that the curcumin-loaded nanoparticles exhibited significantly enhanced cytotoxicity against MCF-7 cell than HEK-293T cells because of the higher cellular uptake efficiency of nanocarriers. More broadly, this work demonstrates a new type of mesoporous silica nanocarrier particularly useful for targeted and controlled drug release applications.