Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with poor prognosis. Insights into the roles of MicroRNAs (miRNAs) in diseases, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches.

Methods: Here, we employed a novel chimeric peptide supramolecular nanoparticle delivery system for plectin-1 (PL-1)-targeted PDAC-specific miR-9 delivery in vitro and in pancreatic cancer patient-derived xenograft (PDX) model. RT-PCR and immunohistochemistry (IHC) were conducted to detect the expression pattern of eIF5A2. mRFP-GFP-LC3 fluorescence microscopy and Western blot were carried out to determine autophagy. Luciferase reporter assays were performed to elucidate the regulatory role of miR-9/eIF5A2 axis.

Results: PL-1/miR-9 nanocomplexes dramatically improve the anticancer effect of doxorubicin through downregulating eIF5A2 expression to inhibit autophagy and induce apoptosis in PDAC therapy in vivo. Mechanistically, miR-9 directly targets the eIF5A2 transcript by binding to its 3'-untranslated region (3'-UTR) to reduce the expression levels and the secreted protein of eIF5A2 in PDAC cells.

Conclusion: PL-1/miR-9 nanoparticles can be used as a novel promising anti-cancer strategy with tumor targeting and miR-9/eIF5A2 may serve as a new potential therapeutic target for future synergic therapy against human PDAC.

胰腺导管腺癌（PDAC）是一种高度致命的疾病，预后不良。对 MicroRNA (miRNA) 在疾病（尤其是癌症）中的作用的深入了解，使 miRNA 成为新型治疗方法的有吸引力的工具和靶标。

方法：在这里，我们采用了一种新型嵌合肽超分子纳米颗粒递送系统，用于体外和胰腺癌患者来源的异种移植（PDX）模型中靶向 plectin-1 (PL-1) 的 PDAC 特异性 miR-9 递送。采用RT-PCR和免疫组织化学（IHC）检测eIF5A2的表达模式。 mRFP-GFP-LC3荧光显微镜和Western blot检测自噬情况。进行荧光素酶报告基因检测以阐明 miR-9/eIF5A2 轴的调节作用。

结果： PL-1/miR-9纳米复合物在体内PDAC治疗中通过下调eIF5A2表达抑制自噬并诱导细胞凋亡，显着提高阿霉素的抗癌效果。从机制上讲，miR-9 通过结合 eIF5A2 的 3'-非翻译区 (3'-UTR) 直接靶向eIF5A2转录本，以降低 PDAC 细胞中 eIF5A2 的表达水平和分泌蛋白。

结论： PL-1/miR-9纳米颗粒可作为一种新型有前景的肿瘤靶向抗癌策略，miR-9/eIF5A2可作为未来针对人PDAC协同治疗的新的潜在治疗靶点。