SS30, a novel thioaptamer targeting CD123, inhibits the growth of acute myeloid leukemia cells

Publication date: 1 September 2019Source: Life Sciences, Volume 232Author(s): Meng Wang, Haibin Wu, Mingyue Duan, Ying Yang, Guoxia Wang, Fengyu Che, Bailing Liu, Wei He, Qiao Li, Liyu ZhangAbstractAimsCD123 represents an important acute myeloid leukemia (AML) therapeutic target. CD123 aptamers may potentially serve as tumor-homing ligands with excellent affinity and specificity for AML targeted therapy, but their complexity, laborious preparation and nuclease digestion limited pharmacological application. The aim of this study was to develop the first CD123 thioaptamer to overcome these obstacles.Main methodsFlow cytometry was utilized to assess the binding specificity, affinity and anti-nuclease ability of thioaptamer. CCK8, Annexin-V/DAPI, and colony forming assays were used to evaluate the anti-cancer ability of thioaptamer in vitro. The tumor volume, weights, survival rate, H&E staining of organs, and serum level of organ damage biomarkers of animal model were applied to investigate the anti-cancer ability of thioaptamer in vivo. Furthermore, we explored the binding mechanism between thioaptamer and CD123.Key findingsCD123 thioaptamer SS30 was able to bind to CD123 structure with high specificity in complex nuclease environment, the dissociation constant of 39.1 nM for CD123 peptide and 287.6 nM for CD123+ AML cells, while exhibiting minimal cross-reactivity to albumin. Furthermore, SS30 inhibited the proliferation and survival of AML cell lines and human AML blasts ...
Source: Life Sciences - Category: Biology Source Type: research

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