Novel nanocarriers for silencing anti-phagocytosis CD47 marker in acute myeloid leukemia cells
Novel nanocarriers for silencing anti-phagocytosis CD47 marker in acute myeloid leukemia cells
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DOI：
10.1016/j.colsurfb.2022.112609
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发表时间：
2022-06-03
影响因子：
5.8
通讯作者：
Zou, Shan
中科院分区：
文献类型：
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作者：
Hassan, Eman M.;Zou, Shan
急性髓性白血病（AML）是一种造血干细胞的恶性疾病，可通过过度表达分化簇47（CD47）标志物来逃避免疫监视，所述分化簇47标志物充当抑制信号，通过与巨噬细胞上的信号调节蛋白α（SIRP α）结合来抑制吞噬作用。AML主要通过化疗治疗，化疗对患者有严重的副作用和不良结局。大多数AML患者会产生耐药性，因此非常需要其他治疗AML的方法。小干扰RNA（siRNA）被认为是一种抗肿瘤治疗剂，因为它能够沉默与过表达的癌症标志物相关的基因，并随后使癌细胞重新敏感。然而，将siRNA递送到细胞中面临挑战，并且期望开发有效的递送系统以在基因水平上成功沉默。在此，我们报告了使用不同配方的氧化石墨烯（GO）作为载体，用于将CD47_siRNA（针对CD47的siRNA）递送到体外AML细胞中。聚乙二醇（PEG）和树枝状大分子（PAMAM）修饰的GO具有小的片状尺寸，实现了抗吞噬标记物CD47基因的最高沉默效率，导致AML细胞中CD47蛋白的下调。此外，使用基于GO的制剂的浓度在AML细胞或正常血细胞中没有显示出细胞毒性，这可用于筛选用于AML靶向基因治疗的潜在药物。
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 alpha (SIRP alpha) 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.