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靶向 ErbB3 癌症治疗:一种有效对抗癌症的协同方法。

Targeted ErbB3 cancer therapy: A synergistic approach to effectively combat cancer.

机构信息

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Marburg, Germany; Faculty of Pharmaceutical Sciences, GC University Faisalabad, Faisalabad, Pakistan.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Marburg, Germany; Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan.

出版信息

Int J Pharm. 2020 Feb 15;575:118961. doi: 10.1016/j.ijpharm.2019.118961. Epub 2019 Dec 14.

Abstract

Surface modification of nanoparticles with aptamer is gaining popularity lately due to its selective targeting and low immunogenicity. In this study, sorafenib tosylate (SFB) was loaded in biodegradable PLGA nanoparticles prepared by solvent evaporation method. The surfaces of drug deprived and drug-loaded particles (PN and PNS, respectively) were coupled with aptamer to target ErbB3 using EDC/NHS chemical modification. Nanoparticles were characterized with regard to their size, shape and chemical composition by dynamic light scattering, atomic force microscopy, FTIR and elemental analysis respectively. To evaluate the particles in vitro cell culture studies were performed. Cell viability assay, pathway analysis and apoptosis assay showed cellular toxicity in the presence of aptamer in PNS-Apt (p < 0.001). Metastatic progression assay showed decreased cell migration in the presence of aptamer and SFB. Confocal laser scanning microscopy was used to visualize the receptor-mediated time-dependent intracellular uptake and distribution of the nanoparticles throughout the cytoplasm. The findings of the current study demonstrated the potential efficacy of the surface modified SFB-loaded particles against ErbB3.

摘要

由于适体具有选择性靶向和低免疫原性,因此最近对纳米颗粒进行适体表面修饰越来越受到关注。在这项研究中,索拉非尼甲苯磺酸盐(SFB)通过溶剂蒸发法制备的可生物降解 PLGA 纳米颗粒中进行装载。通过 EDC/NHS 化学修饰,将药物剥夺和载药颗粒(PN 和 PNS,分别)的表面与适体偶联,以靶向 ErbB3。通过动态光散射、原子力显微镜、FTIR 和元素分析分别对纳米颗粒的大小、形状和化学组成进行了表征。为了评估体外的颗粒,进行了细胞培养研究。细胞活力测定、通路分析和凋亡测定显示,在 PNS-Apt 中存在适体时具有细胞毒性(p<0.001)。转移进展测定显示,在存在适体和 SFB 的情况下,细胞迁移减少。共聚焦激光扫描显微镜用于可视化受体介导的纳米颗粒在细胞质内的时间依赖性细胞内摄取和分布。本研究的结果表明,表面修饰的载 SFB 纳米颗粒对 ErbB3 具有潜在的疗效。

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