Construction of a target MSNs drugcarrier loaded with siRNAGLI1 and siRNASMO aim at hedgehog signal pathway and the pharmacodynamic study of drug-carriers in the treatment of leukemia stem cells.

Abstract

Leukemia stem cells (LSCs) are responsible for leukemia initiation and targeting LSCs is one strategy to treat this disease. This study aims to target LSCs using multi-siRNA loaded antibodies modified with mesoporous silica nanoparticles (MSNs). Here, both siRNAGLI1 and siRNASMO were loaded in an anti-CD34 antibody modified with MSNs, and then, the MSN@siRNAGLI1@Antibody + MSNs@siRNASMO@Antibody cocktail was used to target LSCs. Expression levels of BCL-2 in LSCs were significantly reduced whereas Bax expression was significantly increased after treatment with nano-drug carriers. In addition, these nano-drug carriers also effectively induced the apoptosis of LSCs. The MSNs@siRNAGLI1@Antibody + MSNs@siRNASMO@Antibody cocktail significantly inhibited LSCs. In short, we constructed two target MSN nano-drug carriers where loaded siRNAs can be used in a chemotherapeutic drug cocktail to improve the treatment of leukemia.