Department of Pharmaceutics and Biopharmaceutics, Philipps University of Marburg, Robert-Koch Strasse 4, 35037 Marburg, Germany; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
Department of Pharmaceutics and Biopharmaceutics, Philipps University of Marburg, Robert-Koch Strasse 4, 35037 Marburg, Germany.
Mater Sci Eng C Mater Biol Appl. 2021 Oct;129:112420. doi: 10.1016/j.msec.2021.112420. Epub 2021 Sep 7.
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, HNMR 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.
玉米醇溶蛋白是一种经美国食品和药物管理局（FDA）批准的玉米蛋白，具有可调控的表面性质和制备成纳米材料的可能性。尽管已经对玉米醇溶蛋白基技术进行了广泛的研究，但将玉米醇溶蛋白应用于癌症光动力疗法（PDT）领域的工作却很有限。在这项工作中，我们报告了玉米醇溶蛋白作为天然光敏剂金丝桃素在体外肝癌 PDT 中的载体。通过化学 PEG 化修饰玉米醇溶蛋白，形成 PEG 化玉米醇溶蛋白胶束，并与两种通过卵磷脂/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。傅里叶变换红外光谱（FT-IR）、核磁共振氢谱（HNMR）和高效凝胶渗透色谱-多角度激光散射（HP-SEC MALS）方法用于确认玉米醇溶蛋白的化学 PEG 化。我们开发的玉米醇溶蛋白纳米颗粒和胶束进一步通过光子相关光谱（PCS）和原子力显微镜（AFM）进行了表征。结果表明，胶束化玉米醇溶蛋白中金丝桃素的粒径相对较小，包封率较高。对肝癌细胞（HepG2 细胞）的光毒性表现出所有设计的玉米醇溶蛋白制剂均呈现出剂量依赖性毒性模式。然而，基于金丝桃素的胶束表现出更优异的细胞毒性，这是由于更高的细胞摄取。因此，处理后的 HepG2 细胞表现出更高水平的细胞内生成的 ROS 和线粒体膜电位破坏，从而诱导细胞凋亡。相比之下，设计的金丝桃素制剂在小鼠成纤维细胞 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疏水性金丝桃素在 PDT 中的递送，并为未来癌症治疗的体内和临床应用铺平道路。
