Department of Biochemistry, Albert Einstein College of Medicine, 1301 Morris Park Ave, Bronx, NY, 10461, USA.
Department of Surgery, Duke University School of Medicine, Durham, NC, 27710, USA.
Nat Commun. 2021 Nov 1;12(1):6275. doi: 10.1038/s41467-021-26463-w.
Aptamers represent a potentially important class of ligands for the development of diagnostics and therapeutics. However, it is often difficult to compare the function and specificity of many of these molecules as assay formats and conditions vary greatly. Here, with an interest in developing aptamer targeted therapeutics that could effectively deliver cargoes to cells, we chemically synthesize 15 aptamers that have been reported to target cell surface receptors or cells. Using standardized assay conditions, we assess each aptamer's binding properties on a panel of 11 different cancer cell lines, correlate aptamer binding to antibody controls and use siRNA transfection to validate each aptamer's binding to reported target receptors. Using a subset of these molecules known to be expressed on prostate cancers, we use near-infrared in vivo imaging to assess the tumor localization following intravenous injection. Our data demonstrate some surprising differences in the reported specificity and function for many of these molecules and raise concerns regarding their cell targeting capabilities. They also identify an anti-human transferrin aptamer, Waz, as a robust candidate for targeting prostate cancers and for future development of aptamer-based therapeutics.
适配体是一类具有很大潜力的配体，可用于开发诊断和治疗方法。然而，由于检测方法和条件差异很大，通常很难比较这些分子的功能和特异性。本研究中，我们对能够有效将药物递送到细胞的适配体靶向治疗药物很感兴趣，因此我们化学合成了 15 种已报道靶向细胞表面受体或细胞的适配体。使用标准化的检测条件，我们评估了每个适配体在 11 种不同癌细胞系上的结合特性，将适配体结合与抗体对照进行关联，并使用 siRNA 转染来验证每个适配体与报告的靶受体的结合。使用其中一部分已知在前列腺癌中表达的分子，我们使用近红外体内成像技术来评估静脉注射后的肿瘤定位。我们的数据表明，这些分子的报道特异性和功能存在一些令人惊讶的差异，并对它们的细胞靶向能力提出了质疑。此外，研究还确定了一种抗人转铁蛋白适配体 Waz，作为靶向前列腺癌和未来基于适配体治疗药物开发的强有力候选物。
