Zein nanoparticles as nontoxic delivery system for maytansine in the treatment of non-small cell lung cancer

Abstract

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.

Keywords

• maytansine
• zein
• lung cancer
• nanoparticle
• a549