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Surface tailored zein as a novel delivery system for hypericin: Application in photodynamic therapy
Biomaterials Advances ( IF 5.5 ) Pub Date : 2021-09-07 , DOI: 10.1016/j.msec.2021.112420
Ahmed M Abdelsalam 1 , Ahmed Somaida 2 , Ghazala Ambreen 2 , Abdallah M Ayoub 3 , Imran Tariq 4 , Konrad Engelhardt 2 , Patrick Garidel 5 , Ibrahim Fawaz 2 , Muhammed U Amin 2 , Matthias Wojcik 2 , Udo Bakowsky 2
Affiliation  

Zein is an FDA-approved maize protein featured by its manipulative surface and the possibility of fabrication into nanomaterials. Although extensive research has been carried out in zein-based technology, limited work is available for the application of zein in the field of cancer photodynamic therapy (PDT). In this work, we report zein as a carrier for the natural photosensitizer hypericin in the PDT of hepatocellular carcinoma in vitro. Zein was modified through chemical PEGylation to form PEGylated zein micelles that were compared with two zein nanoparticle formulations physically stabilized by either the lecithin/pluronic mixture or sodium caseinate. FT-IR, 1HNMR and HP-SEC MALS approaches were employed to confirm the chemical PEGylation of zein. Our developed zein nanoparticles and micelles were further characterized by photon correlation spectroscopy (PCS) and atomic force microscopy (AFM). The obtained results showed relatively smaller sizes and higher encapsulation of hypericin in the micellar zein than the nanoparticle-based formulations. Phototoxicity on hepatocellular carcinoma (HepG2 cells) manifested a dose-dependent toxicity pattern of all designed zein formulations. However, superior cytotoxicity was prominent for the hypericin-based micelles, which was influenced by the higher cellular uptake profile. Consequently, the treated HepG2 cells manifested a higher level of intracellular generated ROS and disruption of mitochondrial membrane potential, which induced apoptotic cell death. Comparatively, the designed hypericin formulations indicated lower phototoxicity profile in murine fibroblast L929 cells reflecting their safety on normal cells. Our investigations suggested that the surface-modified zein could be employed to enhance the delivery of the hydrophobic hypericin in PDT and pave the way for future in vivo and clinical applications in cancer treatment.



中文翻译:

表面定制玉米蛋白作为金丝桃素的新型递送系统:在光动力疗法中的应用

玉米蛋白是一种获得 FDA 批准的玉米蛋白,其特点是具有可操作的表面和可制成纳米材料的可能性。尽管基于玉米醇溶蛋白的技术已经进行了广泛的研究,但可用于玉米醇溶蛋白在癌症光动力疗法 (PDT) 领域中的应用的工作有限。在这项工作中,我们报道了玉米醇溶蛋白作为体外肝细胞癌 PDT 中天然光敏剂金丝桃素的载体。玉米醇溶蛋白通过化学聚乙二醇化修饰形成聚乙二醇化的玉米醇溶蛋白胶束,将其与两种通过卵磷脂/普朗尼克混合物或酪蛋白酸钠物理稳定的玉米醇溶蛋白纳米颗粒制剂进行比较。红外光谱,1HNMR 和 HP-SEC MALS 方法用于确认玉米醇溶蛋白的化学聚乙二醇化。我们开发的玉米醇溶蛋白纳米颗粒和胶束通过光子相关光谱 (PCS) 和原子力显微镜 (AFM) 进一步表征。获得的结果表明,与基于纳米颗粒的制剂相比,胶束玉米蛋白中金丝桃素的尺寸相对较小,包封率更高。对肝细胞癌(HepG2 细胞)的光毒性表现出所有设计的玉米醇溶蛋白制剂的剂量依赖性毒性模式。然而,基于金丝桃素的胶束具有优异的细胞毒性,这受到较高细胞摄取特征的影响。因此,处理过的 HepG2 细胞表现出更高水平的细胞内产生的 ROS 和线粒体膜电位的破坏,从而诱导细胞凋亡。相比之下,设计的金丝桃素制剂在鼠成纤维细胞 L929 细胞中表现出较低的光毒性,反映了它们对正常细胞的安全性。我们的研究表明,表面修饰的玉米醇溶蛋白可用于增强 PDT 中疏水性金丝桃素的传递,并为未来在癌症治疗中的体内和临床应用铺平道路。

更新日期:2021-09-16
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