Pancreatic cancer is one of the most lethal malignancies. Treatment with the first-line agent, gemcitabine, is often unsuccessful because it, like other traditional chemotherapeutic agents, is non-specific, resulting in off-target effects that necessitate administration of subcurative doses. Alternatively, monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are highly toxic small molecules that require ligand-targeted delivery. MMAE has already received FDA approval as a component of an anti-CD30 antibody-drug conjugate, brentuximab vedotin. However, in contrast to antibodies, aptamers have distinct advantages. They are chemicals, which allows them to be produced synthetically and facilitates the rapid development of diagnostics and therapeutics with clinical applicability. In addition, their small size allows for enhanced tissue distribution and rapid systemic clearance. Here, we assayed the toxicity of MMAE and MMAF conjugated to an anti-transferrin receptor aptamer, Waz, and an anti-epidermal growth factor receptor aptamer, E07, on the pancreatic cancer cell lines Panc-1, MIA PaCa-2, and BxPC3. In vitro, our results indicate that these aptamers are a viable option for the targeted delivery of toxic payloads to pancreatic cancer cells.

胰腺癌是最致命的恶性肿瘤之一。一线药物吉西他滨的治疗通常是不成功的，因为与其他传统的化学治疗剂一样，吉西他滨是非特异性的，导致脱靶效应，因此需要给予亚治疗剂量。或者，单甲基耳他汀E（MMAE）和单甲基耳他汀F（MMAF）是需要配体靶向递送的剧毒小分子。MMAE作为抗CD30抗体-药物偶联物brentuximab vedotin的组成部分，已经获得FDA的批准。但是，与抗体相比，适体具有明显的优势。它们是化学物质，可以合成生产，并有助于具有临床适用性的诊断和治疗方法的快速发展。此外，它们的小尺寸可增强组织分布和快速的全身清除。在这里，我们测定了与抗运铁蛋白受体适体Waz和抗表皮生长因子受体适体E07偶联的MMAE和MMAF对胰腺癌细胞系Panc-1，MIA PaCa-2和BxPC3的毒性。在体外，我们的结果表明，这些适体是将有毒有效载荷靶向递送至胰腺癌细胞的可行选择。