Abstract
The objective of this study was to construct norcantharidin (NCTD)/tetrandrine (Tet) dual-drug loaded lipid nanoparticles (FA-LP@Tet/(MSNs@NCTD)) based on mesoporous silica nanoparticles (MSNs) for controlling drug release and lowering their systemic toxicity. In this study, MSNs were prepared and used for encapsulating anticancer drug NCTD; then MSNs@NCTD and Tet were loaded into liposomes to construct dual-drug loaded lipid nanoparticles with folic acid (FA) as the targeting moiety. The prepared dual-drug loaded lipid nanoparticles with a uniform particle size distribution of 153.17±4.17 nm (PDI 0.191±0.017, zeta potential -20.93±1.75 mV), had a visible core-shell structure under transmission electron microscopy; the encapsulation efficiency of NCTD and Tet was 86.62% and 79.19%, respectively, with obvious in vitro sustained release characteristics. The cellular uptake results suggested that FA modification could enhance intracellular distribution of FA-LP@Tet/(MSNs@NCTD). Furthermore, cell apoptosis assays showed FA-LP@Tet/(MSNs@NCTD) had better antitumor ability via reversing multidrug resistance. Therefore, FA-LP@Tet/(MSNs@NCTD) was a promising drug delivery system for combination cancer therapy.
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