Colorectal carcinoma is a complex disease accounting for adenoma tumors and an aggressive phenotype, and the third leading cause of cancer death. In the past decades, miRNAs have been associated with molecular pathways of cancer and other diseases. The dysregulated miRNAs play an inhibitory or promoting role in tumorigenesis. Therefore, restoration of tumor-suppressed microRNAs (miRNA) may offer novel therapeutic approaches for cancer treatment. Nevertheless, the poor bioavailability of miRNA due to their rapid enzymatic degradation is a critical barrier in cancer gene therapy. To overcome this dilemma, we designed disulfide cross-linking micelles (DCM) nanocarrier for delivery of miR-145 to colon cancer cells and investigated its therapeutic efficacy in vitro and in vivo. Results indicated that the presence of DCM nanocarrier loaded with miR-145 enhanced selective delivery of miR-145 and facilitated cellular uptake, significantly up-regulating miR-145 expression in HCT-116 cell lines. Consequently, the cell proliferation was inhibited by arresting cell cycle at the G1 phase. Further, apoptosis of HCT-116 cells treated with miR-145 complex nanoparticles may be via downregulation of oncogenes MYC and FSCN1, predicting regulatory targets for miR-145. These results pave the way for further investigations into the potential of miR-145 complex nanocarrier for cancer gene therapy.

中文翻译：

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通过下调MYC和FSCN1在结肠癌细胞中的二硫键交联胶束纳米载体加载的miR-145传递系统的抑制。

大肠癌是导致腺瘤肿瘤和侵袭性表型的复杂疾病，是导致癌症死亡的第三大原因。在过去的几十年中，miRNA已与癌症和其他疾病的分子途径相关。失调的miRNA在肿瘤发生中起抑制或促进作用。因此，恢复肿瘤抑制的microRNA（miRNA）可能为癌症治疗提供新的治疗方法。然而，由于miRNA的快速酶促降解，其生物利​​用度差是癌症基因治疗中的关键障碍。为了克服这一难题，我们设计了用于递送的miR-145的二硫键交联胶束（DCM）纳米载体到结肠癌细胞，并研究其治疗功效的体外和体内。结果表明，装载有miR-145的DCM纳米载体的存在增强了miR-145的选择性递送并促进了细胞摄取，从而显着上调了HCT-116细胞系中miR-145的表达。因此，通过将细胞周期停滞在G1期来抑制细胞增殖。此外，用miR-145复合纳米颗粒处理的HCT-116细胞的凋亡可能是通过癌基因MYC和FSCN1的下调，从而预测了miR-145的调控靶标。这些结果为进一步研究miR-145复合纳米载体在癌症基因治疗中的潜力铺平了道路。