A model of lipoplex-induced peritonitis was used to characterize the inflammatory response to cationic lipid:DNA lipoplexes with respect to activation of host antitumoral effector mechanisms. Three different cationic lipids were used in these studies: N,N-dioleyl-N,N-dimethylammonium chloride (DODAC), N-(1-[2,3-dioleoyloxy]propyl)-N,N,N-trimethylammonium chloride (DOTAP), and N-(1-[2,3-dioleyloxy]propyl)-N,N,N-trimethylammonium chloride (DOTMA). The DODAC and DOTMA lipoplexes exhibited similar transfection properties in vitro, whereas the DOTAP lipoplexes transfected quite poorly in all cell lines tested. Intraperitoneal injection of cationic lipoplexes into immunocompetent mice resulted in a profound infiltration of inflammatory cells, secretion of interferon-γ, and increased natural killer activity within the peritoneal cavity. Both DODAC and DOTMA lipoplexes produced similar inflammatory responses, lasting at least 5 days. The inflammation induced by DOTAP lipoplexes peaked by day 3 and resolved to near-control levels by day 5. These data indicate that although cationic lipid DNA complexes may differ in their inflammatory properties, the natural killer activation and interferon-γ secretion that follow lipoplex administration should provide a functional adjuvant for cancer gene therapies that benefit from immunostimulation.
About this article
Cite this article
Bramson, J., Bodner, C. & Graham, R. Activation of host antitumoral responses by cationic lipid/DNA complexes. Cancer Gene Ther 7, 353–359 (2000). https://doi.org/10.1038/sj.cgt.7700143
- Cationic liposome
- gene therapy.
Cationic Liposome/DNA Complexes Mediate Antitumor Immunotherapy by Promoting Immunogenic Tumor Cell Death and Dendritic Cell Activation
ACS Applied Materials & Interfaces (2020)
Cationic lipid/pDNA complex formation as potential generic method to generate specific IRF pathway stimulators
European Journal of Pharmaceutics and Biopharmaceutics (2020)
International Journal of Molecular Sciences (2015)
Transferrin lipoplex-mediated suicide gene therapy of oral squamous cell carcinoma in an immunocompetent murine model and mechanisms involved in the antitumoral response
Cancer Gene Therapy (2009)
Molecular Therapy (2007)