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HA-Modified R8-Based Bola-Amphiphile Nanocomplexes for Effective Improvement of siRNA Delivery Efficiency
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2020-03-30 , DOI: 10.1021/acsbiomaterials.0c00231
Nan Jia 1 , Jingjing Ma 1 , Yan Gao 1 , Haiyang Hu 1 , Dawei Chen 1 , Xiuli Zhao 1 , Yue Yuan 1 , Mingxi Qiao 1
Affiliation  

The development of new nonviral vectors with high transfection efficiency and low cyto-toxicity remains a great challenge in the field of small interfering RNA delivery. To address the challenge, we developed two cationic amphiphilic carriers, octa-arginine double-substituted (R8-bibola) and octa-arginine monosubstituted (R8-monobola), based on transmembrane peptide-octa-arginine (R8) for complexing siRNA (R8-bola/siRNA). To further improve the stability of the nanocomplexes and tumor targeting, HA-R8-bola/siRNA nanocomplexes were prepared by surface modification of R8-bola/siRNA with hyaluronic acid (HA). In vitro experiments showed that R8-bibola has better biocompatibility than R8-monobola, which effectively increased the cell uptake of siRNA and improved the Bcl-2 protein silencing efficiency. In vivo antitumor experiments confirmed that the HA-modified nanocomplexes effectively inhibited tumor growth by silencing Bcl-2 protein expression. The new bola-type nanoparticles provide a new strategy to improve the delivery efficiency of siRNA for tumor treatment.

中文翻译:

HA修饰的基于R8的Bola-两亲纳米复合物可有效提高siRNA的输送效率

在小干扰RNA递送领域中,具有高转染效率和低细胞毒性的新的非病毒载体的开发仍然是巨大的挑战。为了解决这一挑战,我们基于跨膜肽-八-精氨酸(R8)开发了两种阳离子两亲性载体,即八-精氨酸双取代(R8-bibola)和八-精氨酸单取代(R8-bibola),用于使siRNA(R8 -bola / siRNA)。为了进一步改善纳米复合物的稳定性和靶向肿瘤,通过用透明质酸(HA)对R8-bola / siRNA进行表面修饰来制备HA-R8-bola / siRNA纳米复合物。体外实验表明,R8-bibola具有比R8-monobola更好的生物相容性,可有效增加siRNA的细胞摄取并提高Bcl-2蛋白的沉默效率。体内抗肿瘤实验证实,HA修饰的纳米复合物通过沉默Bcl-2蛋白表达来有效抑制肿瘤生长。新的bola型纳米颗粒提供了提高siRNA肿瘤治疗效率的新策略。
更新日期:2020-04-23
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