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负载吡咯替尼的曲妥珠单抗功能化SK-BR-3细胞膜包裹的介孔二氧化硅纳米颗粒用于HER-2阳性乳腺癌的靶向治疗

Trastuzumab-functionalized SK-BR-3 cell membrane-wrapped mesoporous silica nanoparticles loaded with pyrotinib for the targeted therapy of HER-2-positive breast cancer.

作者信息

Liu Xing, Shen Wenwen

机构信息

The First Affiliated Hospital of Jinzhou Medical University, No.2, The Fifth Section of Renmin Street, Guta District, Jinzhou, Liaoning Province 121001, China.

出版信息

Int J Pharm X. 2024 Nov 14;8:100302. doi: 10.1016/j.ijpx.2024.100302. eCollection 2024 Dec.

Abstract

In this study, the trastuzumab-functionalized SK-BR-3 cell membrane-wrapped mesoporous silica nanoparticles loaded with pyrotinib (Tra-CM-MSN-PYR) were prepared for targeted therapy of HER2-positive breast cancer. Transmission electron microscopy (TEM) characterization showed that MSN had a spherical morphology with mesoporous channels and that the structure of Tra-CM-MSN was a cell membrane (CM) layer successfully coated on the surface of MSN. A cellular uptake assay demonstrated that FITC-labeled Tra-CM-MSN were taken up by SK-BR-3 breast cancer cells, which illustrated that Tra-CM-MSN had good targeting ability compared with CM-MSN and MSN. In vivo imaging experiments demonstrated significant accumulation of FITC-labeled Tra-CM-MSN in tumor tissues, further proving that Tra-CM-MSN have superior targeting properties. Cell apoptosis experiments suggested that Tra-CM-MSN-PYR significantly inhibited the proliferation of SK-BR-3 breast cancer cells. The results of in vivo animal experiments also showed that Tra-CM-MSN-PYR significantly inhibited tumor growth. These results indicate that Tra-CM-MSN-PYR has potential application as a targeted therapy for HER2-positive breast cancer in the future.

摘要

在本研究中,制备了负载吡咯替尼的曲妥珠单抗功能化的SK-BR-3细胞膜包裹的介孔二氧化硅纳米颗粒(Tra-CM-MSN-PYR),用于HER2阳性乳腺癌的靶向治疗。透射电子显微镜(TEM)表征显示,介孔二氧化硅纳米颗粒(MSN)呈球形且具有介孔通道,Tra-CM-MSN的结构是在MSN表面成功包覆了一层细胞膜(CM)。细胞摄取实验表明,SK-BR-3乳腺癌细胞摄取了异硫氰酸荧光素(FITC)标记的Tra-CM-MSN,这说明与CM-MSN和MSN相比,Tra-CM-MSN具有良好的靶向能力。体内成像实验表明,FITC标记的Tra-CM-MSN在肿瘤组织中显著蓄积,进一步证明Tra-CM-MSN具有优异的靶向特性。细胞凋亡实验表明,Tra-CM-MSN-PYR显著抑制SK-BR-3乳腺癌细胞的增殖。体内动物实验结果还显示,Tra-CM-MSN-PYR显著抑制肿瘤生长。这些结果表明,Tra-CM-MSN-PYR在未来作为HER2阳性乳腺癌的靶向治疗具有潜在应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e93b/11609682/617e3d3528e9/ga1.jpg

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