Delivery of RIPK4 small interfering RNA for bladder cancer therapy using natural halloysite nanotubes
Delivery of RIPK4 small interfering RNA for bladder cancer therapy using natural halloysite nanotubes
复制标题
使用天然埃洛石纳米管递送 RIPK4 小干扰 RNA 用于膀胱癌治疗
DOI：
10.1126/sciadv.aaw6499
复制
发表时间：
2019-09-01
期刊：
影响因子：
13.6
通讯作者：
Cao, Ke
中科院分区：
文献类型：
--
作者：
Liu, Jianye;Zhang, Yi;Cao, Ke
HNTs/siRIPK 4纳米颗粒已被证明是膀胱癌的有效治疗方法。RNA干扰（RNAi）技术可以特异性沉默靶基因的表达，并已成为治疗癌症的一种有前途的治疗方法。在本研究中，我们发现天然埃洛石纳米管（HNT）辅助递送靶向受体相互作用蛋白激酶4（RIPK 4）的活性小干扰RNA（siRNA）有效地沉默其表达以治疗膀胱癌。HNTs/siRNA复合物增加了siRNA的血清稳定性，增加了其在血液中的循环寿命，并促进了siRNA的细胞摄取和肿瘤积累。siRNA显著下调膀胱癌细胞和膀胱肿瘤中的RIPK 4表达，从而抑制三种膀胱肿瘤模型（皮下模型、原位膀胱肿瘤模型和肺转移模型）中的肿瘤发生和进展，并且没有不良反应。因此，我们揭示了使用RIPK 4沉默来抑制膀胱癌的简单但有效的方法，表明膀胱癌的有希望的治疗方法。
HNTs/siRIPK4 nanoparticles have been shown to be an effective treatment for bladder cancer. RNA interference (RNAi) technology can specifically silence the expression of a target gene and has emerged as a promising therapeutic method to treat cancer. In the present study, we showed that natural halloysite nanotube (HNT)–assisted delivery of an active small interfering RNA (siRNA) targeting receptor-interacting protein kinase 4 (RIPK4) efficiently silenced its expression to treat bladder cancer. The HNTs/siRNA complex increased the serum stability of the siRNA, increased its circulation lifetime in blood, and promoted the cellular uptake and tumor accumulation of the siRNA. The siRNA markedly down-regulated RIPK4 expression in bladder cancer cells and bladder tumors, thus inhibiting tumorigenesis and progression in three bladder tumor models (a subcutaneous model, an in situ bladder tumor model, and a lung metastasis model), with no adverse effects. Thus, we revealed a simple but effective method to inhibit bladder cancer using RIPK4 silencing, indicating a promising therapeutic method for bladder cancer.