Although microRNAs (miRNAs)-based cancer therapy strategies have been proved to be efficient and superior to chemotherapeutic agents in certain extent, the unstable properties of miRNAs significantly impaired the wide application. Therefore, how to safely deliver the miRNAs to the targeted site of action is the most pivotal step to achieve the ideal treatment effect. In the present work, the miR-128-3p, which is able of inducing chromosomal instability, was loaded into the nanocomplexes developed by the PEG-PDMAEMA (PDMAEMA-NP). By this way, the miR-128-3p was shielded from exposure to various degrading enzymes in bloodstream. Additionally, the PEGylation endowed the PDMAEMA-NP with long time of circulation as demonstrated in vivo by pharmacokinetics investigation. To target and deliver the miR-128-3p to the site of action, a tumor-homing peptide CPKSNNGVC, which specifically targets the monocarboxylate transporter 1 (MCT1), was decorated on the surface of PDMAEMA-NP. Both in vitro and in vivo experiments demonstrated that more efficient delivery of miR-128-3p to cells or tumor tissues was obtained by the PDMAEMA-NP than plasmid. Additionally, modification of C peptides further enhanced the tumor accumulation of miR-128-3p, and in turn contributed to the stronger tumor growth inhibition effect. Underlying mechanisms study revealed that the miR-128-3p inhibited the growth, migration, and invasion of colorectal cancer (CRC) cells and progress of CRC tissues through silence of the activity of PI3K/AKT and MEK/ERK pathway. By this way, the chemotherapy effect of 5-Fluorouracil (5-Fu) was dramatically improved after co-treating the cells with miR-128-3p formulations.

中文翻译：

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载有miR-128-3p的纳米复合物可通过双重靶向沉默PI3K / AKT和MEK / ERK途径增强结直肠癌的化疗效果。

尽管已证明基于microRNA（miRNA）的癌症治疗策略在一定程度上是有效且优于化学治疗剂的，但miRNA的不稳定特性显着损害了其广泛应用。因此，如何安全地将miRNA传递至目标作用位点是实现理想治疗效果的最关键步骤。在目前的工作中，将能够诱导染色体不稳定性的miR-128-3p装入由PEG-PDMAEMA（PDMAEMA-NP）开发的纳米复合物中。通过这种方式，miR-128-3p避免暴露于血液中的各种降解酶。另外，如体内通过药代动力学研究证明的，PEG化使PDMAEMA-NP具有较长的循环时间。为了将miR-128-3p定位并交付到行动地点，在PDMAEMA-NP的表面上修饰了一个肿瘤靶向肽CPKSNNGVC，它专门针对单羧酸盐转运蛋白1（MCT1）。体外和体内实验均表明，与质粒相比，PDMAEMA-NP能更有效地将miR-128-3p传递至细胞或肿瘤组织。另外，C肽的修饰进一步增强了miR-128-3p的肿瘤蓄积，进而有助于更强的肿瘤生长抑制作用。潜在的机制研究表明，miR-128-3p通过沉默PI3K / AKT和MEK / ERK途径抑制了结直肠癌（CRC）细胞的生长，迁移和侵袭以及CRC组织的进展。通过这种方式，将细胞与miR-128-3p制剂共处理后，5-氟尿嘧啶（5-Fu）的化疗效果得到了显着改善。