Folic acid modified lipid-bilayer coated mesoporous silica nanoparticles co-loading paclitaxel and tanshinone IIA for the treatment of acute promyelocytic leukemia

Abstract

In this work, paclitaxel (Ptx) combined with tanshinone IIA (TanIIA) was found to show synergistic effect on inducing apoptosis of human acute promyelocytic leukemia (APL) cell line NB4, and the anti-tumor effect was strongest when its molar ratio was 1:1. To enhance the efficacy and reduce side effects, an active targeting drug delivery system with mesoporous silica nanoparticles (MSNs) coated with folic acid (FA) modified PEGylated lipid-bilayer (LB) membrane (FA-LB-MSNs) was established for co-loading drugs. The drug loadings of Ptx and TanIIA in FA-LB-MSNs were 5.5% and 1.8%, respectively. Compared with the uncoated MSNs, the FA-LB-MSNs showed a sustained drug release, and Ptx and TanIIA released synchronously from the carriers. By means of biological adhesion between FA and its receptors, the uptake of FA-LB-MSNs by NB4 cells was significantly higher than that of uncoated preparations, and Ptx combined with TanIIA had strong synergistic effect to enhance the apoptosis and differentiation of NB4 cells. The results of pharmacodynamics in vivo showed that the FA-LB-MSNs targeted tumor in nude mice more effectively than the compared formulations without FA modification. The Ptx and TanIIA-loaded FA-LB-MSNs group showed significantly better effects on inducing apoptosis and inhibiting tumor growth than the reference groups, which agreed with the results of anti-tumor experiments in vitro. Furthermore, no toxicity was observed to the heart, liver, spleen, lung and kidney of the tumor-bearing animals, indicating good biocompatibility of the prepared novel nanocarriers. This study confirmed the synergistic therapeutic effect of Ptx and TanIIA on APL, and the superior of FA-LB-MSNs as co-loaded nanocarriers for active targeted therapy of tumors.