Purpose: Maytansine (DM1) is a potent anticancer drug and limited in clinical application due to its poor water solubility and toxic side effects. Zein is widely used in nano drug delivery systems due to its good biocompatibility. In this study, we prepared DM1-loaded zein nanoparticles (ZNPs) to achieve tumor targeting and reduce toxic side effects of DM1. Methods: ZNPs were prepared by phase separation and Box-Behnken design was used to optimize the formulation. Then, confocal fluorescence microscope and flow cytometry were used to determine cellular uptake of ZNPs. A549 cells were cultured in vitro to study cytotoxicity and used to establish tumor xenografts in nude mice. Biodistribution and antitumor activity of ZNPs were performed in vivo experiments. In addition, we also performed histological and immunohistochemical examinations on tumors and viscera. Results: The optimal prescription was obtained by using 120 μL zein added to 2 mL water under stirring in 300 rpm. The encapsulation efficiency and drug loading were 82.97 ± 0.80% and 3.32 ± 0.03%, respectively. We found that DM1-loaded ZNPs have a strong inhibitory effect on A549 cells, which stemmed from the ability of ZNPs to enhance cellular uptake. Furthermore, we demonstrated that DM1-loaded ZNPs exhibits a better antitumor efficacy than DM1, which tumor inhibition rate were 97.3% and 92.7%, respectively. The biodistribution revealed that ZNPs could targeted to tumor. Finally, we confirmed by histological that DM1-loaded ZNPs are nontoxic. Conclusion: DM1-loaded ZNPs have considerable antitumor activity. Thus, DM1-loaded ZNPs are a promising treatment of non-small cell lung cancer.

中文翻译：

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玉米醇溶蛋白纳米颗粒作为美登素在非小细胞肺癌治疗中的无毒递送系统。

目的：美登素（DM1）是一种有效的抗癌药物，由于其水溶性差和毒性副作用而在临床上受到限制。玉米蛋白因其良好的生物相容性而广泛用于纳米药物递送系统。在这项研究中，我们制备了加载DM1的玉米醇溶蛋白纳米颗粒（ZNPs），以实现肿瘤靶向并减少DM1的毒副作用。方法：采用相分离法制备ZNPs，采用Box-Behnken设计优化配方。然后，使用共聚焦荧光显微镜和流式细胞仪确定ZNPs的细胞摄取。在体外培养A549细胞以研究细胞毒性，并用于在裸鼠中建立肿瘤异种移植物。ZNP的生物分布和抗肿瘤活性在体内实验中进行。此外，我们还对肿瘤和内脏进行了组织学和免疫组化检查。结果：最佳处方是通过在300 rpm搅拌下将120μL玉米醇溶蛋白添加到2 mL水中获得的。包封效率和载药量分别为82.97±0.80％和3.32±0.03％。我们发现，加载DM1的ZNP对A549细胞具有很强的抑制作用，这源于ZNP增强细胞摄取的能力。此外，我们证明了加载DM1的ZNPs表现出比DM1更好的抗肿瘤功效，其肿瘤抑制率分别为97.3％和92.7％。生物分布表明ZNP可以靶向肿瘤。最后，我们通过组织学证实了DM1加载的ZNP是无毒的。结论：加载DM1的ZNP具有相当大的抗肿瘤活性。从而，