Nano-liposomal zein hydrolysate for improved apoptotic activity and therapeutic index in lung cancer treatment

Drug Deliv. 2022 Dec;29(1):1049-1059. doi: 10.1080/10717544.2022.2057618.

Abstract

Lung cancer is one of the most common cancers in the world with a high mortality rate. Zein is a protein compound whose protein isolate is not useful and whose protein hydrolysis produces biological activity. By encapsulating this bioactive compound inside the nanoparticles (NPs), it causes itself to reach the tumor site and destroy it rapidly. In this study, the effects of zein hydrolysate (ZH) and nano-liposomal ZH (N-ZH) were investigated on the human A549 cell line. Western blotting and cell cycle analyses showed that ZH and N-ZH caused cytotoxicity. They induced apoptosis via cell cycle arrest at the G0 phase, as well as significant increases in pro-apoptotic genes, such as Bax, caspase-3, -8, -9, and p53, accompanied with significant decreases in the anti-apoptotic marker Bcl-2. Based on the results, the cytotoxic and anticancer effects of N-ZH were higher than those of free ZH. In conclusion, liposomes improved the performance of ZH and dramatically reduced the IC50 value of ZH. These findings provided the experimental evidence that N-ZH with favorable anticancer activity can be used as a therapeutic agent and strategy for lung cancer treatment in future clinical trials.

Keywords: Liposome; apoptosis; hydrolysate; lung cancer; zein.

MeSH terms

  • Apoptosis
  • Humans
  • Liposomes / pharmacology
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • Therapeutic Index
  • Zein*

Substances

  • Liposomes
  • Zein

Grants and funding

This work was financially supported by grants from the Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran [Grant No. 63810]. This work was also supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) [grant numbers 2019R1A5A2027340 and 2021R1A2C2007937]. This work was supported by a grant (21153MFDS607) from Ministry of Food and Drug Safety of South Korea in 2021-2025.