Novel cationic polyene glycol phospholipids as DNA transfer reagents—Lack of a structure–activity relationship due to uncontrolled self-assembling processes
| Autor: | Muhammad Zeeshan, Michael D. Pungente, Philip L. Leopold, David G. Nicholson, Vassilia Partali, Natalia Bilchuk, Howard H. Lou, Liji Raju, Nada Abdul Khalique, Christer L. Øpstad, Asma Zaidi, Aleksandra Liberska, Helge B. Larsen, Marcella Flinterman, Chinmay Surve, Emile Jubeli, Mitchell A. Izower, Hans-Richard Sliwka |
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| Rok vydání: | 2014 |
| Předmět: |
Stereochemistry
Phospholipid CHO Cells Polyenes Transfection Biochemistry Glycols Structure-Activity Relationship Surface-Active Agents chemistry.chemical_compound Cricetulus Cations Cricetinae Amphiphile Animals Structure–activity relationship Molecular Biology Alkyl chemistry.chemical_classification Liposome Organic Chemistry Cationic polymerization DNA Cell Biology Polyene Combinatorial chemistry chemistry Liposomes Indicators and Reagents lipids (amino acids peptides and proteins) Crystallization |
| Zdroj: | Chemistry and Physics of Lipids. 183:117-136 |
| ISSN: | 0009-3084 |
| DOI: | 10.1016/j.chemphyslip.2014.04.006 |
| Popis: | Cationic glycol phospholipids were synthesized introducing chromophoric, rigid polyenoic C20:5 and C30:9 chains next to saturated flexible alkyl chains of variable lengths C6-20:0. Surface properties and liposome formation of the amphiphilic compounds were determined, the properties of liposome/DNA complexes (lipoplexes) were established using three formulations (no co-lipid, DOPE as a co-lipid, or cholesterol as a co-lipid), and the microstructure of the best transfecting compounds inspected using small angle X-ray diffraction to explore details of the partially ordered structures of the systems that constitute the series. Transfection and cytotoxicity of the lipoplexes were evaluated by DNA delivery to Chinese hamster ovary (CHO-K1) cells using the cationic glycerol phospholipid 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPC) as a reference compound. The uncontrollable self-association of the molecules in water resulted in aggregates and liposomes of quite different sizes without a structure–property relationship. Likewise, adding DNA to the liposomes gave rise to unpredictable sized lipoplexes, which, again, transfected without a structure–activity relationship. Nevertheless, one compound among the novel lipids (C30:9 chain paired with a C20:0 chain) exhibited comparable transfection efficiency and toxicity to the control cationic lipid EPC. Thus, the presence of a rigid polyene chain in this best performing achiral glycol lipid did not have an influence on transfection compared with the chiral glycerolipid reference ethyl phosphocholine EPC with two flexible saturated C14 chains. |
| Databáze: | OpenAIRE |
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