Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Adv Drug Deliv Rev. 2015 Jan;81:34-52. doi: 10.1016/j.addr.2014.09.006. Epub 2014 Sep 22.
Pancreatic ductal adenocarcinoma (PDAC) is a severe pancreatic malignancy and is predicted to victimize 1.5% of men and women during their lifetime (Cancer statistics: SEER stat fact sheet, National Cancer Institute, 2014). miRNAs have emerged as a promising prognostic, diagnostic and therapeutic tool to fight against pancreatic cancer. miRNAs could modulate gene expression by imperfect base-pairing with target mRNA and hence provide means to fine-tune multiple genes simultaneously and alter various signaling pathways associated with the disease. This exceptional miRNA feature has provided a paradigm shift from the conventional one drug one target concept to one drug multiple target theory. However, in vivo miRNA delivery is not fully realized due to challenges posed by this special class of therapeutic molecules, which involves thorough understanding of the biogenesis and physicochemical properties of miRNA and delivery carriers along with the pathophysiology of the PDAC. This review highlights the delivery strategies of miRNA modulators (mimic/inhibitor) in cancer with special emphasis on PDAC since successful delivery of miRNA in vivo constitutes the major challenge in clinical translation of this promising class of therapeutics.
胰腺导管腺癌（PDAC）是一种严重的胰腺恶性肿瘤，预计在其一生中会使 1.5%的男性和女性受害（癌症统计：SEER 统计情况说明书，国家癌症研究所，2014 年）。miRNAs 已成为对抗胰腺癌有前途的预后、诊断和治疗工具。miRNAs 可以通过与靶 mRNA 的不完全碱基配对来调节基因表达，从而提供同时微调多个基因和改变与疾病相关的各种信号通路的手段。这种特殊的 miRNA 特征提供了从传统的一种药物一个靶标概念到一种药物多个靶标理论的范式转变。然而，由于这一类治疗分子所带来的挑战，体内 miRNA 的传递尚未完全实现，这涉及到对 miRNA 和递药载体的生物发生和物理化学特性以及 PDAC 的病理生理学的深入了解。这篇综述强调了 miRNA 调节剂（模拟物/抑制剂）在癌症中的传递策略，特别强调了 PDAC，因为在体内成功传递 miRNA 是这一有前途的治疗药物临床转化的主要挑战。
