期刊
PHARMACEUTICS
卷 13, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics13050729
关键词
non-viral gene delivery; gemini cationic lipid; transfection; protein corona; interleukin-12; pro-inflammatory cytokine
资金
- Spanish Ministry of Science, Innovation and Universities (MICIU) [RTI2018-095844-B-I00, RTI2018-097609-B-C22]
- University Complutense of Madrid (Spain) [UCMA05-33-010, GR2019/2020-910447, GR29/20]
- Regional Government of Madrid [P2018/NMT-4389]
- PE I + D+i 2013-2016 - ISCIII [PT17/0019]
- ERDF
The study demonstrates the efficient transfection of plasmid DNA encoding IL-12 into cells using a combination of gemini cationic lipids and zwitterionic helper lipids as nanovectors. The nanovectors show high cell viability and adsorb beneficial proteins on their surface, making them promising candidates for future in vivo applications of pCMV-IL12 transfection.
Ample evidence exists on the role of interleukin-12 (IL-12) in the response against many pathogens, as well as on its remarkable antitumor properties. However, the unexpected toxicity and disappointing results in some clinical trials are prompting the design of new strategies and/or vectors for IL-12 delivery. This study was conceived to further endorse the use of gemini cationic lipids (GCLs) in combination with zwitterionic helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanol amine) as nanovectors for the insertion of plasmid DNA encoding for IL-12 (pCMV-IL12) into cells. Optimal GCL formulations previously reported by us were selected for IL-12-based biophysical experiments. In vitro studies demonstrated efficient pCMV-IL12 transfection by GCLs with comparable or superior cytokine levels than those obtained with commercial control Lipofectamine2000*. Furthermore, the nanovectors did not present significant toxicity, showing high cell viability values. The proteins adsorbed on the nanovector surface were found to be mostly lipoproteins and serum albumin, which are both beneficial to increase the blood circulation time. These outstanding results are accompanied by an initial physicochemical characterization to confirm DNA compaction and protection by the lipid mixture. Although further studies would be necessary, the present GCLs exhibit promising characteristics as candidates for pCMV-IL12 transfection in future in vivo applications.
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