Cationic Nanoparticles Containing Cationic Peptide Cargo Synergistically Induce Cellular Reactive Oxygen Species and Cell Death in HepG2 Cells

  • Chul-Ho Yun
  • Chun-Sik Bae
  • Taeho AhnEmail author


Previous reports have suggested that cationic nanoparticles (NPs)-consisting of cationic monovalent lipids, such as 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), induce reactive oxygen species (ROS) and ROS-mediated toxicity in cells. We have investigated the effects of DOTAP-based NPs (dNPs) containing cationic peptide (cPep) cargo on HepG2 cells. Compared with cargo-free dNPs, treatment with cPep-dNPs containing peptides composed of lysine (or arginine) residues further stimulated the production of cellular ROS. Concomitantly, the cell viability was more decreased by the treatment with cPep-dNPs. A cationic peptide composed of 6–10 lysine residues showed the most effective synergistic induction of ROS. However, dNPs encapsulating neutral peptide consisted of alanine residues did not elicit synergistic ROS generation or cell death. The present study suggests that a cationic peptide-NP system might effectively induce cancer cell death through the production of ROS in the absence of any other therapeutic cancer reagents.


DOTAP DOTMA HepG2 Nanoparticle Cationic peptide Reactive oxygen species 



This research was carried out with the support of Veterinary Biochemical Practice Program for undergraduate students 2014–2017, Chonnam National University.

Compliance with Ethical Standards

Conflict of interest

The authors declares that they have no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. Bhagwat SV, Vijayasarathy C, Raza H, Mullick J, Avadhani NG (1998) Preferential effects of nicotine and 4-(N-methyl-N-nitrosamine)-1-(3-pyridyl)-1-butanone on mitochondrial glutathione S-transferase A4-4 induction and increased oxidative stress in the rat brain. Biochem Pharmacol 56:831–839CrossRefGoogle Scholar
  2. Böhlen P, Stein S, Dairman W, Udenfriend S (1973) Fluorometric assay of proteins in the nanogram range. Arch Biochem Biophys 155:213–220CrossRefGoogle Scholar
  3. Chen Y, Bathula SR, Yang Q, Huang L (2010) Targeted nanoparticles deliver siRNA to melanoma. J Invest Dermatol 130:2780–2798Google Scholar
  4. Dokka S, Toledo D, Shi X, Castranova V, Rojanasakul Y (2000) Oxygen radical-mediated pulmonary toxicity induced by some cationic liposomes. Pharm Res 17:521–525CrossRefGoogle Scholar
  5. Fernandez-Lopez S, Kim HS, Choi EC, Delgado M, Grania JR, Khasanov A, Kraehenbuehl K, Long G, Weinberger DA, Wilcoxen KM, Ghadiri MR (2001) Antibacterial agents based on the cyclic d,l-α-peptide architecture. Nature 412:452–455CrossRefGoogle Scholar
  6. Iwaoka S, Nakamura T, Takano S, Tsuchiya S, Aramaki Y (2006) Cationic liposomes induce apoptosis through p38 MAP kinase-casepase-8-Bid pathway in macrophage-like RAW264.7 cells. J Leukoc Biol 79:184–191CrossRefGoogle Scholar
  7. Podesta JE, Kostarelos K (2009) Engineering cationic liposome siRNA complexes for in vitro and in vivo delivery. Methods Enzymol 464:343–354CrossRefGoogle Scholar
  8. Sadhu SS, Wang S, Dachineni R, Averineni RK, Yang Y, Yin H, Bhat GJ, Guan X (2017) In vitro and in vivo tumor growth inhibition by glutathione disulfide liposomes. Cancer Growth Metastasis. Google Scholar
  9. Shai Y (2002) Mode of action of membrane active antimicrobial peptides. Biopolymers 66:236–248CrossRefGoogle Scholar
  10. Szoka F Jr, Papahadjopoulos D (1978) Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci USA 75:4194–4198CrossRefGoogle Scholar
  11. Vasievich EA, Ramishetti S, Zhang Y, Huang L (2012) Trp2 peptide vaccine adjuvanted with (R)-DOTAP inhibits tumor growth in an advanced melanoma model. Mol Pharm 9:261–268CrossRefGoogle Scholar
  12. Wang Y, Miao L, Satterlee A, Huang L (2015) Delivery of oligonucleotides with lipid nanoparticles. Adv Drug Deliv Rev 87:68–80CrossRefGoogle Scholar
  13. Yan W, Chen W, Huang L (2008) Reactive oxygen species play a central role in the activity of cationic liposome based cancer vaccine. J Control Release 130:22–28CrossRefGoogle Scholar
  14. Yang Y, Cao J, Shi Y (2004) Identification and characterization of a gene encoding human LPGAT1, an endoplasmic reticulum-associated lysophosphatidylglycerol acyltransferase. J Biol Chem 279:55866–55874CrossRefGoogle Scholar
  15. Yun CH, Bae CS, Ahn T (2016) Cargo-free nanoparticles containing cationic lipids induce reactive oxygen species and cell death in HepG2 cells. Biol Pharm Bull 39:1338–1346CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Biological Sciences and TechnologyChonnam National UniversityGwangjuRepublic of Korea
  2. 2.College of Veterinary MedicineChonnam National UniversityGwangjuRepublic of Korea

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