Amelioration of Colorectal Cancer Using Negative Lipidoid Nanoparticles to Encapsulate siRNA Against APRIL by Enema Delivery Mode
Amelioration of Colorectal Cancer Using Negative Lipidoid Nanoparticles to Encapsulate siRNA Against APRIL by Enema Delivery Mode
复制标题
使用负类脂质纳米颗粒通过灌肠递送模式封装针对 APRIL 的 siRNA 来改善结直肠癌
DOI：
10.1007/s12253-014-9779-5
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发表时间：
2014-10-01
影响因子：
2.8
通讯作者：
Wang, Huimin
中科院分区：
文献类型：
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作者：
Ding, Weifeng;Wang, Guihua;Wang, Huimin
增殖诱导配体(APRIL)是一种关键的细胞增殖调节分子，在免疫调节和一些免疫性疾病中已经得到了很好的研究。APRIL可刺激肿瘤细胞生长，并在肿瘤组织中上调表达，尤其是在结直肠癌组织中。然而，抑制APRIL是否能够在体内调节肿瘤相关基因的表达，从而改善结直肠癌的病理进程仍不清楚。为了解决这个问题，我们开发了一种新型的负性类脂纳米粒(NLN)，它包裹了小干扰RNA(SiRNA)，用于选择性沉默体内结直肠癌病灶实质中的APRIL，摄取通过脂筏内吞途径进行。局部灌肠给予APRIL-NLN可使结直肠癌细胞和动物模型中的APRIL沉默，并通过抑制结直肠癌细胞的增殖、转移和凋亡相关细胞因子的表达而在实验上改善结直肠癌的进展，且不影响肝肾功能，也不触发结直肠癌模型的免疫反应。这项研究通过体内实验揭示了APRIL是一个潜在的抗结直肠癌靶点，并表明类似的siRNA递送模式在其他治疗环境中的应用可能是可行的。
A proliferation-inducing ligand (APRIL) is a key cell proliferation-regulatory molecule and have been investigated well enough in immunity regulation and a few of immune diseases. APRIL can stimulate tumor cell growth and is up-expressed in cancer tissues, especially in CRC (colorectal cancer). However, whether inhibition of APRIL can regulate tumor-relative genes expression in vivo and subsequently ameliorate the pathological progress of CRC remains obscure. To address this question, we developed a novel negative lipidoid nanoparticles (NLNs) encapsulating small interference RNA (siRNA) for selectively silencing APRIL in the parenchyma of CRC focus in vivo, which uptake proceeded through a lipid raft endocytotic pathway. Local enema delivery of APRIL-NLNs silenced APRIL in CRC cells and animal models, and then ameliorated experimentally the progress of CRC by suppressing CRC cell proliferation, metastasis, and apoptosis-related cytokine expression and did not affect the function of liver and kidneys and not trigger the immune response of CRC models. This study reveals APRIL to be a potential anti-CRC target by in vivo experiments, and suggests that the application of similar modes of siRNA delivery may be feasible in other therapeutic settings.