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Encapsulation of Apoptotic Proteins in Lipid Nanoparticles to Induce Death of Cancer Cells

Abstract

According to previous reports, cationic nanoparticles (cNPs) consisting of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), a cationic lipid, without any cargos, induce generation of reactive oxygen species (ROS) and toxicity in cells. We investigated the effect of DOTAP-based cNPs containing encapsulated human pro-apoptotic proteins (P-cNPs), tBid, Bax, or cytochrome c (Cyt c) on the death of HepG2, cancer cells. Upon the treatment to cells, cNPs containing Cyt c-cargo were the most effective in inducing cell death, followed by tBid- and Bax-cNPs. Among three P-cNPs, Cyt c-cNPs also induced the highest levels of ROS production and caspase-3 activity in the cells under the treatment with the same DOTAP concentration. The incorporation of dioleoylglycerol (DOG), a neutral phospholipid, in cNPs at the expense of DOTAP resulted in an increased amount of the encapsulated protein and consequently enhanced cell death in a DOG concentration-dependent manner. Thus, the present cNP formulation with protein cargo may elicit apoptotic effects in cancer cells and serve as a rational background for the preparation of cationic lipid-based NP formulation for cancer treatment.

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Abbreviations

DAG:

1,2-diacyl-sn-glycerol

DOG:

1,2-dioleoylglycerol

DOPC:

1,2-dioleoyl-3-phosphocholine

DOPE:

1,2-dioleoyl-3-phosphoethanolamine

DOTAP:

1,2-dioleoyl-3-trimethylammonium-propane

GAPDH:

glyceraldehyde 3-phosphate dehydrogenase

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

ROS:

reactive oxygen species

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Acknowledgments

This study was financially supported by Chonnam National University (Grant number: 2018-3390, C.-S. Bae) and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1D1A1B03034829).

The authors declare no conflict of interest.

Neither ethical approval nor informed consent was required for this study.

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Correspondence to Taeho Ahn.

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Bae, CS., Lee, CM. & Ahn, T. Encapsulation of Apoptotic Proteins in Lipid Nanoparticles to Induce Death of Cancer Cells. Biotechnol Bioproc E 25, 264–271 (2020). https://doi.org/10.1007/s12257-019-0409-7

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Keywords

  • apoptosis
  • cell death
  • cytochrome c
  • DOTAP
  • nanoparticle
  • reactive oxygen species