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Identification of a DNA Aptamer That Binds to Human Monocytes and Macrophages.
Bioconjugate Chemistry ( IF 4.7 ) Pub Date : 2020-06-26 , DOI: 10.1021/acs.bioconjchem.0c00247
Meilyn Sylvestre 1 , Christopher P Saxby 1 , Nataly Kacherovsky 1 , Heather Gustafson 1 , Stephen J Salipante 2 , Suzie H Pun 1
Affiliation  

As cancer strategies shift toward immunotherapy, the need for new binding ligands to target and isolate specific immune cell populations has soared. Based on prior work identifying a peptide specific for murine M2-like macrophages, we sought to identify an aptamer that could bind human M2-like macrophages. Tumor-associated macrophages (TAMs) adopt an M2-like phenotype and support tumor progression and dissemination. Here, we employed cell-SELEX to identify an aptamer ligand that targets this cell population over tissue resident (M0-like) or tumoricidal (M1-like) macrophages. Instead, we identified an aptamer that binds both human M0- and M2-like macrophages and monocytes, with highest binding affinity to M2-like macrophage (Kd ∼ 20 nM) and monocytes (Kd ∼ 45 nM) and minimal binding to other leukocytes. The aptamer binds to CD14+ but not CD16+ monocytes, and is rapidly internalized by these cells. We also demonstrate that this aptamer is able to bind human monocytes when both are administered in vivo to mice. Thus, binding to these cell populations (monocytes, M0-like and M2-like macrophages), this aptamer lends itself toward monocyte-specific applications, such as monocyte-targeted drug delivery or column selection.

中文翻译:

与人单核细胞和巨噬细胞结合的DNA适体的鉴定。

随着癌症策略转向免疫疗法,对靶向和分离特定免疫细胞群的新结合配体的需求激增。基于鉴定鼠类M2巨噬细胞特异性肽的先前工作,我们寻求鉴定可结合人M2样巨噬细胞的适体。肿瘤相关巨噬细胞(TAM)采用M2类表型,并支持肿瘤的进展和扩散。在这里,我们采用细胞SELEX来识别适体配体,该适体配体针对组织常驻(M0样)或杀肿瘤(M1样)巨噬细胞上的该细胞群。相反,我们鉴定适体,其结合人和M0-和M2样巨噬细胞和单核细胞,以最高结合亲和力M2状巨噬细胞(ķ d〜20 nM)的和单核细胞(ķ d约45 nM),与其他白细胞的结合极少。适体结合CD14 +但不结合CD16 +单核细胞,并被这些细胞迅速内在化。我们还证明了,当两者在体内给予小鼠时,该适体能够结合人单核细胞。因此,该适体与这些细胞群(单核细胞,M0样和M2样巨噬细胞)结合,使其适合于单核细胞特异性应用,例如靶向单核细胞的药物递送或色谱柱选择。
更新日期:2020-08-19
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