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

Signaling pathways governing the behaviors of leukemia stem cells

“… 126 , 127 Moreover, mesoporous silica nanoparticles carrying siRNA GLI1 and siRNA SMO have been shown to facilitate LSCs' apoptosis and may be regarded as a chemotherapeutic drug cocktail to manage leukemia. 128 …”

The role of Hedgehog and Notch signaling pathway in cancer

“…2. Ligand dependency: (i) Auto-secretory ligand-dependent activation, in which tumor cells respond to increased expression of their HH ligands in a cell-autonomous manner (i.e., glioblastoma [ 201 ], neck squamous cell carcinoma [ 202 , 203 ], and lung [ 204 ], breast [ 205 , 206 ], ovarian [ 207 ], stomach [ 208 , 209 ], esophageal [ 210 ], pancreatic [ 211 ], and prostate cancers); (ii) Paracrine-ligand-dependent model, in which Hh ligands produced and released by tumor cells switch on HH signaling in the peripheral stroma, in turn facilitating tumor expansion and metastasis, and creating a positive feedback loop (i.e., prostate, ovarian [ 212 – 214 ], pancreatic [ 215 ] and colorectal cancers [ 216 , 217 ]); (iii) Reverse paracrine ligand-dependent signaling activation, indicates that Hh ligands are secreted from the stroma and received by tumor cells (i.e., multiple myeloma, lymphoma [ 218 ], and leukemia [ 219 , 220 ]). 3.…”