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。
Targeted delivery of anti-miR-155 by functionalized mesoporous silica nanoparticles for colorectal cancer therapy.
机构信息
Department of Hepatobiliary and Pancreas Surgery, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen 518020, China.
Department of Emergency, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen 518020, China.
出版信息
Int J Nanomedicine. 2018 Mar 1;13:1241-1256. doi: 10.2147/IJN.S158290. eCollection 2018.
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。
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