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miR-559 的分子印迹于肽固定的聚 L-多巴/二氧化硅核壳上及其对 HER2 阳性乳腺癌细胞的体外作用研究。

Molecular imprinting of miR-559 on a peptide-immobilized poly L-DOPA/silica core-shell and in vitro investigating its effects on HER2-positive breast cancer cells.

机构信息

Department of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.

Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran.

出版信息

Drug Deliv Transl Res. 2023 Oct;13(10):2487-2502. doi: 10.1007/s13346-023-01330-x. Epub 2023 Mar 29.

Abstract

In a significant percentage of breast cancers, increased expression of the HER2 receptor is seen and is associated with the spread and worsening of the disease. This research aims to investigate the effect of miR-559 (which targets HER2 mRNA) on SKBR3 breast cancer cells and the possibility of their effective delivery with polymeric nanoparticles and tumor-targeting peptides. L-DOPA monomers were polymerized on the surface of silica nanoparticles in the presence of miR-559 (as a molecular template for molecular imprinting) then an anti-HER2 peptide coupled to the surface of these polymeric nanocomposites (miR-NC-NL2), and the effects of this construct against a HER2-positive breast cancer cells (SKBR3 cells) investigated in vitro conditions. The results showed that miR-NC-NL2 is selective for HER2-positive cells and delivers the miR-559 to them in a targeted manner. miR-NC-NL2 decreased the proliferation of SKBR3 cells and reduced the expression and production of HER2 protein in these cells. Effective and targeted delivery of miR-559 to HER2-positive cancer cells by the miR-NC-NL2 promises the therapeutic potential of this nascent structure based on its inhibitory effect on cancer growth and progression. Of course, animal experiments require a better understanding of this structure's anti-tumor effects.

摘要

在相当大比例的乳腺癌中,HER2 受体的表达增加,并与疾病的扩散和恶化有关。本研究旨在探讨 miR-559(靶向 HER2 mRNA)对 SKBR3 乳腺癌细胞的影响,以及用聚合物纳米粒子和肿瘤靶向肽有效递送至这些细胞的可能性。在 miR-559(作为分子印迹的分子模板)的存在下,将 L-DOPA 单体聚合在硅纳米粒子的表面,然后将抗 HER2 肽偶联到这些聚合物纳米复合材料的表面(miR-NC-NL2),并在体外条件下研究该构建体对 HER2 阳性乳腺癌细胞(SKBR3 细胞)的作用。结果表明,miR-NC-NL2 对 HER2 阳性细胞具有选择性,并以靶向方式将 miR-559 递送至这些细胞。miR-NC-NL2 降低了 SKBR3 细胞的增殖,并减少了这些细胞中 HER2 蛋白的表达和产生。miR-NC-NL2 能够有效靶向递送至 HER2 阳性癌细胞的 miR-559,有望基于其对癌症生长和进展的抑制作用,为这种新兴结构带来治疗潜力。当然,动物实验需要更好地了解这种结构的抗肿瘤作用。

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