Novel nanocarriers for silencing anti-phagocytosis CD47 marker in acute myeloid leukemia cells

Abstract

Acute myeloid leukemia (AML), a malignant disorder of Hematopoietic stem cells, can escape immunosurveillance by over expression of the cluster of differentiation 47 (CD47) marker, which functions as an inhibitory signal, suppressing phagocytosis by binding to signal regulatory protein α (SIRPα) on macrophages. AML is treated mainly by chemotherapy, which has drastic side effects and poor outcomes for the patients. Most AML patients develop drug resistance, so other methods to treat AML are highly required. Small interfering RNA (siRNA) is considered as an antitumor therapeutic due to its ability to silence genes associated with the overexpressed cancer markers and subsequently re-sensitize cancer cells. However, delivering siRNA into cells faces challenges, and the development of an effective delivery system is desired for successful silencing at the gene level. Herein, we report the usage of different formulations of graphene oxide (GO) as carriers for the delivery of CD47_siRNA (siRNA against CD47) into AML cells in vitro. The polyethylene glycol (PEG) and dendrimers (PAMAM) modified GO with small flake sizes achieved the highest silencing efficiency of the anti-phagocytosis marker CD47 gene, resulted CD47 protein down-regulation in AML cells. Moreover, the concentration at which the GO-based formulations was used has shown no cytotoxicity in AML cells or normal blood cells, which could be used to screen potential drugs for targeted gene therapy in AML.