[Basic Research on Therapy of Leukemia with Nanoparticles Drug Delivery System Modified by Transferrin Receptor Monoclonal Antibody].

Abstract

To investigate the therapeutic effect of targeted drug-loaded nanoparticles modified by transferrin receptor monoclonal antibody (TfR mAb) on acute leukemia and its potential anti-tumor mechanism. Nanoparticles drug delivery system, which was composed of poly (lactic-co-glycolic acid), poly-l-lysine, polyethylene glycol, TfR mAb (TfR mAb-PLGA-PLL-PEG)-daunorubicin (DNR), was first synthesized. After drug intervention, the intracellular accumulation in leukemia HL60 cells was observed under a fluorescent microscope and concentration of DNR was determined by flow cytometry (FCM). Meanwhile, cell apoptosis rate was measured by FCM and the expression levels of apoptosis related protein Cleaved-caspase 3 was determined by Western blot. Under an inverted fluorescent microscope, intracellular accumulation of DNR autofluorescence in HL60 cells was observed in both TfR mAb-PLGA-PLL-PEG-DNR group and DNR group. FCM analysis showed that the intracellular concentration of DNR in TfR mAb-PLGA-PLL-PEG-DNR group was higher than that in DNR group（P<0.05）. The apoptotic rate of HL60 cells in TfR mAb-PLGA-PLL-PEG-DNR group was higher than that of DNR group（P<0.05）. Moreover, the expression levels of apoptosis-related protein Cleaved-caspase 3 in TfR mAb-PLGA-PLL-PEG-DNR group was significantly higher than that in DNR group（P<0.05）. TfR mAb-PLGA-PLL-PEG nanoparticle drug delivery system can target chemotherapy drugs to leukemia cells and enhance anticancer ability through apoptotic pathway.