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抗体功能化 Cubosomes 作为治疗 HER2 阳性乳腺癌的潜在策略。

Cubosomes functionalized with antibodies as a potential strategy for the treatment of HER2-positive breast cancer.

机构信息

Department of Health Sciences and Technology, ETH Zurich, 8092 Zurich, Switzerland.

Paul Scherrer Institute (PSI), 5232 Villigen, Switzerland.

出版信息

J Colloid Interface Sci. 2024 Nov;673:291-300. doi: 10.1016/j.jcis.2024.06.091. Epub 2024 Jun 11.

Abstract

Breast cancers that overexpress human epidermal growth factor receptor 2 (HER2) have poor prognosis. Moreover, available chemotherapies cause numerous side effects due to poor selectivity. To advance more effective and safer therapies for HER2-positive breast cancer, we explored the fusion of drug delivery technology and immunotherapy. Our research led to the design of immunocubosomes loaded with panobinostat and functionalized with trastuzumab antibodies, enabling precise targeting of breast cancer cells that overexpress HER2. We characterised the nanostructure of cubosomes using small-angle X-ray scattering (SAXS), cryo-transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS). Moreover, we confirmed the integrity of the trastuzumab antibodies on the immunocubosomes by Fourier-transform infrared spectroscopy (FTIR) and sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Additionally, we found that panobinostat-loaded immunocubosomes were more cytotoxic, and in an uptake-dependant manner, towards a HER2-positive breast cancer cell line (SKBR3) compared to a cell line representing healthy cells (L929). These results support that the functionalization of cubosomes with antibodies enhances both the effectiveness of the loaded drug and its selectivity for targeting HER2-positive breast cancer cells.

摘要

过表达人表皮生长因子受体 2(HER2)的乳腺癌预后不良。此外,由于选择性差,现有的化疗药物会引起许多副作用。为了推进更有效和更安全的 HER2 阳性乳腺癌治疗方法,我们探索了药物传递技术和免疫疗法的融合。我们的研究导致了载有 panobinostat 的免疫立方体制剂的设计,并通过曲妥珠单抗抗体进行功能化,从而能够精确靶向过表达 HER2 的乳腺癌细胞。我们使用小角 X 射线散射(SAXS)、冷冻透射电子显微镜(cryo-TEM)和动态光散射(DLS)来描述立方体制剂的纳米结构。此外,我们通过傅里叶变换红外光谱(FTIR)和十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS-PAGE)证实了免疫立方体制剂上曲妥珠单抗抗体的完整性。此外,我们发现与代表健康细胞的细胞系(L929)相比,载有 panobinostat 的免疫立方体制剂对 HER2 阳性乳腺癌细胞系(SKBR3)的细胞毒性更强,且呈摄取依赖性。这些结果表明,用抗体对立方体制剂进行功能化可以提高载药的有效性及其对 HER2 阳性乳腺癌细胞的选择性。

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