Ternary Nanoparticles with a Sheddable Shell Efficiently Deliver MicroRNA-34a against CD44-Positive Melanoma,Molecular Pharmaceutics

当前位置： X-MOL 学术 › Mol. Pharmaceutics › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Ternary Nanoparticles with a Sheddable Shell Efficiently Deliver MicroRNA-34a against CD44-Positive Melanoma
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-08-14 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00377
Minmin Fan _{1,

2} , Ye Zeng ₁ , Huitong Ruan ₁ , Zhirong Zhang ₁ , Tao Gong ₁ , Xun Sun ₁

Affiliation

PEGylation can stabilize drug delivery systems for cancer therapy by creating repulsive interactions with biological components in vivo. While these interactions reduce nonspecific adsorption of drug-loaded particles onto nontarget surfaces, they also inhibit internalization of particles into target cells. To circumvent this so-called “PEG-dilemma”, we have developed nanoparticles with a PEG coating that is shed after arrival in target tissue. Positively charged polycation nanoparticles were assembled with microRNA-34a via electrostatic interactions and then coated again via electrostatic interactions with an anionic PEG derivative that separates from the nanoparticle in the acidic tumor microenvironment. The resulting ternary nanoparticles with a sheddable shell have nearly neutral surface charge, which markedly reduces nonspecific adsorption. Shedding the PEG coat enhanced nanoparticle uptake into CD44-positive melanoma cells and promoted microRNA-34a release, which down-regulated CD44 expression and thereby inhibited tumor growth. We conclude that nanocarriers with a sheddable shell show promise for cancer therapy.

中文翻译：

具有可剥壳的三元纳米粒子有效地交付针对CD44阳性黑色素瘤的MicroRNA-34a。

聚乙二醇化可以通过与体内生物成分产生排斥性相互作用来稳定用于癌症治疗的药物输送系统。尽管这些相互作用减少了载药颗粒在非靶标表面上的非特异性吸附，但它们也抑制了颗粒向靶标细胞内化。为了避免这种所谓的“ PEG困境”，我们开发了带有PEG涂层的纳米颗粒，该涂层在到达目标组织后脱落。带正电荷的聚阳离子纳米颗粒通过静电相互作用与microRNA-34a组装在一起，然后通过静电相互作用再次用与酸性肿瘤微环境中与纳米颗粒分离的阴离子PEG衍生物包覆。所得的具有可脱落壳的三元纳米颗粒具有几乎中性的表面电荷，这显着降低了非特异性吸附。剥开PEG涂层可增强纳米颗粒对CD44阳性黑色素瘤细胞的摄取，并促进microRNA-34a的释放，它下调了CD44的表达，从而抑制了肿瘤的生长。我们得出的结论是，具有可脱落外壳的纳米载体显示出有望用于癌症治疗。

更新日期：2017-08-15

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11