Background

The use of RNA interference (iRNA) therapy has proved to be an interesting target therapy for the cancer treatment; however, siRNAs are unstable and quickly eliminated from the bloodstream. To face these barriers, the use of biocompatible and efficient nanocarriers emerges as an alternative to improve the success application of iRNA to the cancer, including breast cancer.

Results

A hybrid nanocarrier composed of calcium phosphate as the inorganic phase and a block copolymer containing polyanions as organic phase, named HNPs, was developed to deliver VEGF siRNA into metastatic breast cancer in mice. The particles presented a rounded shape by TEM images with average size measured by DLS suitable and biocompatible for biomedical applications. The XPS and EDS spectra confirmed the hybrid composition of the nanoparticles. Moreover, after intravenous administration, the particles accumulated mainly in the tumor site and kidneys, which demonstrates the tumor targeting accumulation through the Enhanced Permeability and Retention Effect (EPR). A significant decrease in size of the tumors treated with the nanoparticles containing siVEGF (HNPs-siVEGF) was observed and the reduction was related to enhanced tumor accumulation of siRNA as well as in vivo VEGF silencing at gene and protein levels.

Conclusion

The hybrid system prepared was successful in promoting the RNAi effect in vivo with very low toxicity.

General significance

This study shows the valuable development of a hybrid nanoparticle carrying VEGF siRNA, as well as their tumor targeting, accumulation and reduction in mice triple-negative breast cancer.

中文翻译：

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由靶向 VEGF 的混合纳米颗粒递送的短干扰 RNA：生物分布和抗肿瘤作用

背景

使用 RNA 干扰 (iRNA) 疗法已被证明是一种有趣的癌症治疗靶标疗法；然而，siRNAs 不稳定，会很快从血流中清除。为了面对这些障碍，使用生物相容性和高效的纳米载体作为一种替代方法出现，以提高 iRNA 在癌症（包括乳腺癌）中的成功应用。

结果

开发了一种由磷酸钙作为无机相和含有聚阴离子作为有机相的嵌段共聚物组成的混合纳米载体，称为 HNP，用于将 VEGF siRNA 递送到小鼠的转移性乳腺癌中。颗粒通过 TEM 图像呈现圆形形状，平均尺寸由 DLS 测量，适用于生物医学应用且具有生物相容性。XPS 和 EDS 光谱证实了纳米颗粒的混合组成。此外，静脉给药后，颗粒主要积聚在肿瘤部位和肾脏，这表明通过增强的渗透性和保留效应（EPR）进行肿瘤靶向积聚。基因和蛋白质水平的体内VEGF 沉默。

结论

制备的混合系统成功地在体内促进了 RNAi 效应，并且毒性非常低。

一般意义

这项研究显示了携带 VEGF siRNA 的混合纳米颗粒的宝贵发展，以及它们在小鼠三阴性乳腺癌中的肿瘤靶向、积累和减少。