功能化介孔硅纳米颗粒靶向递送抗 miR-155 用于结直肠癌治疗。

INTRODUCTION: MicroRNA-155 (miR-155) is an oncogenic microRNA, which is upregulated in many human cancers including colorectal cancer (CRC). Overexpression of miR-155 has been found to regulate several cancer-related pathways, and therefore, targeting miR-155 may be an effective strategy for cancer therapy. However, effective and safe delivery of anti-miR-155 to tumors remains challenging for the clinical applications of anti-miR-155-based therapeutics. METHODS: In this study, we explored the expression of miR-155 and the transcription factor nuclear factor kappa B (NF-κB) in CRC tissues and cell lines, and the possible relationship between miR-155 and NF-κB. We further report on anti-miR-155-loaded mesoporous silica nanoparticles (MSNs) modified with polymerized dopamine (PDA) and AS1411 aptamer (MSNs-anti-miR-155@PDA-Apt) for the targeted treatment of CRC. RESULTS: Results showed that miR-155 is overexpressed in CRC tissues and cell lines, and there is a positive feedback loop between NF-κB and miR-155. Compared to the control groups, MSNs-anti-miR-155@PDA-Apt could efficiently downregulate miR-155 expression in SW480 cells and achieve significantly high targeting efficiency and enhanced therapeutic effects in both in vivo and in vitro experiments. Furthermore, inhibition of miR-155 by MSNs-anti-miR-155@PDA-Apt can enhance the sensitivity of SW480 to 5-fluorouracil chemotherapy. CONCLUSION: Thus, our results suggested that MSNs-anti-miR-155@PDA-Apt is a promising nanoformulation for CRC treatment.

简介：微小 RNA-155（miR-155）是一种致癌微小 RNA，在包括结直肠癌（CRC）在内的许多人类癌症中上调。miR-155 的过表达已被发现调节几种与癌症相关的途径，因此，靶向 miR-155 可能是癌症治疗的有效策略。然而，miR-155 的有效和安全递送到肿瘤对于基于 miR-155 的治疗剂的临床应用仍然具有挑战性。

方法：在这项研究中，我们探索了 miR-155 和转录因子核因子 kappa B（NF-κB）在 CRC 组织和细胞系中的表达，以及 miR-155 和 NF-κB 之间的可能关系。我们进一步报告了载有抗 miR-155 的介孔硅纳米粒子（MSNs），其用聚合多巴胺（PDA）和 AS1411 适体（MSNs-anti-miR-155@PDA-Apt）进行修饰，用于 CRC 的靶向治疗。

结果：结果表明，miR-155 在 CRC 组织和细胞系中过度表达，并且 NF-κB 和 miR-155 之间存在正反馈回路。与对照组相比，MSNs-anti-miR-155@PDA-Apt 能够在 SW480 细胞中有效地下调 miR-155 的表达，并在体内和体外实验中实现显著的高靶向效率和增强的治疗效果。此外，MSNs-anti-miR-155@PDA-Apt 通过抑制 miR-155 可以增强 SW480 对 5-氟尿嘧啶化疗的敏感性。

结论：因此，我们的结果表明，MSNs-anti-miR-155@PDA-Apt 是治疗 CRC 的一种有前途的纳米制剂。