Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12
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-1...
| Authors: | ; ; ; ; ; ; |
|---|---|
| Format: | Article |
| Publication date: | 2021 |
| Country: | España |
| Institution: | Universidad Complutense de Madrid (UCM) |
| Repository: | Docta Complutense |
| Language: | English |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/108994 |
| Online Access: | https://hdl.handle.net/20.500.14352/108994 |
| Access Level: | Open access |
| Keyword: | 544 577.1 Non-viral gene delivery Gemini cationic lipid Transfection Protein corona Interleukin-12 Pro-inflammatory cytokine Química física (Química) Bioquímica (Química) 2307 Química Física 2302.26 Bioquímica Física |
| _version_ | 1878741674823254016 |
|---|---|
| author | Sánchez Arribas, Natalia |
| author2 | Martínez Negro, María Aicart, Clara Tros de Ilarduya, Conchita Aicart Sospedra, Emilio Guerrero Martínez, Andrés Junquera González, María Elena |
| author2_role | author author author author author author |
| author_browse | Aicart Sospedra, Emilio Aicart, Clara Guerrero Martínez, Andrés Junquera González, María Elena Martínez Negro, María Sánchez Arribas, Natalia Tros de Ilarduya, Conchita |
| author_facet | Sánchez Arribas, Natalia Martínez Negro, María Aicart, Clara Tros de Ilarduya, Conchita Aicart Sospedra, Emilio Guerrero Martínez, Andrés Junquera González, María Elena |
| author_role | author |
| collection | Docta Complutense |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_e96801f57d42d1d2a1f55e06e4e7fdf0 |
| institution | Universidad Complutense de Madrid (UCM) |
| instname_str | Universidad Complutense de Madrid (UCM) |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:docta.ucm.es:20.500.14352/108994 |
| publishDate | 2021 |
| publishDateSort | 2021 |
| publisher | MDPI |
| publisherStr | MDPI |
| reponame_str | Docta Complutense |
| spelling | Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12 Sánchez Arribas, Natalia Martínez Negro, María Aicart, Clara Tros de Ilarduya, Conchita Aicart Sospedra, Emilio Guerrero Martínez, Andrés Junquera González, María Elena 544 577.1 Non-viral gene delivery Gemini cationic lipid Transfection Protein corona Interleukin-12 Pro-inflammatory cytokine Química física (Química) Bioquímica (Química) 2307 Química Física 2302.26 Bioquímica Física 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. MDPI https://hdl.handle.net/20.500.14352/108994 |
| spellingShingle | Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12 Sánchez Arribas, Natalia 544 577.1 Non-viral gene delivery Gemini cationic lipid Transfection Protein corona Interleukin-12 Pro-inflammatory cytokine Química física (Química) Bioquímica (Química) 2307 Química Física 2302.26 Bioquímica Física |
| title | Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12 |
| title_full | Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12 |
| title_fullStr | Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12 |
| title_full_unstemmed | Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12 |
| title_short | Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12 |
| title_sort | Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12 |
| topic | 544 577.1 Non-viral gene delivery Gemini cationic lipid Transfection Protein corona Interleukin-12 Pro-inflammatory cytokine Química física (Química) Bioquímica (Química) 2307 Química Física 2302.26 Bioquímica Física |
| topic_facet | 544 577.1 Non-viral gene delivery Gemini cationic lipid Transfection Protein corona Interleukin-12 Pro-inflammatory cytokine Química física (Química) Bioquímica (Química) 2307 Química Física 2302.26 Bioquímica Física |
| url | https://hdl.handle.net/20.500.14352/108994 |