AbCD133 Modified αCT1 Loaded Target Magnetic Mesoporous Silica Nano-Drugcarriers Can Sensitizes Glioma Cancer Stem Cells to TMZ and Have Therapeutic Potential on TMZ Resistant Glioblastoma

: Glioblastoma (GBM) is the most common and aggressive primary brain tumor, temozolomide (TMZ) is widely used for the treatment of GBM, but the effects of TMZ for GBM are limited by the presence of rapid resistance. It was reported that a small percentage of glioma cells which called glioma stem cells (GSCs) lead GBM resistance to TMZ, and sensitizes GSCs to TMZ was an effective way to solve the TMZ resistance and cure the GBM. A polypeptide αCT1 is selective inhibitor of connexin43 (Cx43) channels which can sensitizes GSCs to TMZ. However, in clinical, the biodegradation of peptides and non-targeting greatly affect the efficacy of polypeptide. Magnetic mesoporous silica nanoparticles (MMSNs) is a very effective peptide drug carrier in which peptides were loaded into its porous structure prevent protease degradation and the drugs can be concentrated in the tumor area without diffusion within a magnetic field. CD133 was a cell marker of GSCs which CD133 can be used in target treatment of GSCs. In this study, we aim to treat TMZ resistant gliomas. The αCT1 and CD133 antibody were first loaded on the MMSNs to construct a target MMSNs drug carrier, the MMSNs constructed here have good biocompatibility, drug loading capacity and release properties. The drug nano-carriers prepared here can enter the GSCs through endocytosis effectively, the results indicated that the combination of MMSNs@ αCT1@AbCD133 and TMZ can block the protein kinase B (AKT)/AMP-activated protein kinase (AMPK)/AMP-activated protein kinase (MTOR) signaling pathway of GSCs and then induce autophagy, apoptosis and the death of GSCs, MMSNs@ αCT1@AbCD133 and TMZ combination also can inhibit the growth of solid tumor. In short, this study indicated that MMSNs@ αCT1@AbCD133 prepared here can sensitizes GSCs to TMZ, combination of MMSNs@ αCT1@AbCD133 and TMZ can be used in treatment of GSCs, we hoped that this study can provide a new way for eradication treatment.