Department of Pharmaceutical Sciences, Federal University of Santa Catarina, SC, Brazil.
Graduate Program in Materials Science and Engineering, Department of Physics, Federal University of Santa Catarina, SC, Brazil.
Biochim Biophys Acta Gen Subj. 2021 Sep;1865(9):129938. doi: 10.1016/j.bbagen.2021.129938. Epub 2021 May 29.
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.
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.
The hybrid system prepared was successful in promoting the RNAi effect in vivo with very low toxicity.
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.
RNA 干扰（iRNA）疗法已被证明是癌症治疗的一种有前途的靶向治疗方法；然而，siRNA 不稳定，容易从血液中迅速消除。为了克服这些障碍，使用生物相容性和高效的纳米载体作为替代方案来提高 iRNA 在癌症（包括乳腺癌）中的成功应用。
开发了一种由磷酸钙作为无机相和含有聚阴离子的嵌段共聚物作为有机相组成的混合纳米载体，称为 HNPs，用于将 VEGF siRNA 递送至小鼠转移性乳腺癌。TEM 图像显示粒子呈圆形，通过 DLS 测量的平均粒径适合且具有生物相容性，适用于生物医学应用。XPS 和 EDS 光谱证实了纳米粒子的混合组成。此外，静脉给药后，粒子主要积聚在肿瘤部位和肾脏中，这表明通过增强的通透性和保留效应（EPR）实现了肿瘤靶向积聚。用含有 siVEGF 的纳米粒子（HNPs-siVEGF）治疗的肿瘤明显缩小，这种减少与 siRNA 的肿瘤积累增强以及体内 VEGF 基因和蛋白水平的沉默有关。
所制备的混合系统成功地在体内促进了 RNAi 效应，而且毒性非常低。
本研究展示了携带 VEGF siRNA 的混合纳米粒子的有价值的开发，以及它们在三阴性乳腺癌小鼠中的肿瘤靶向性、积累和减少。
