Polyene-based cationic lipids as visually traceable siRNA transfer reagents
| Autor: | Muhammad Zeeshan, Vassilia Partali, Philip L. Leopold, Natalia Bilchuk, Hans-Richard Sliwka, Liji Raju, Emile Jubeli, Cory Zegel, Agape Chen, Christer L. Øpstad, Michael D. Pungente, Nada Abdul Khalique, Howard H. Lou |
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| Rok vydání: | 2015 |
| Předmět: |
Chemistry
Pharmaceutical Genetic Vectors Pharmaceutical Science Excipient Polyenes Gene delivery Transfection chemistry.chemical_compound Cations Cell Line Tumor medicine Humans Cationic liposome RNA Small Interfering Luciferases Phospholipids Alkyl chemistry.chemical_classification Liposome Gene Transfer Techniques Cationic polymerization General Medicine Polyene Lipids chemistry Biochemistry Liposomes Nucleic acid Biophysics Indicators and Reagents lipids (amino acids peptides and proteins) HeLa Cells Biotechnology medicine.drug |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 89:280-289 |
| ISSN: | 0939-6411 |
| DOI: | 10.1016/j.ejpb.2014.12.011 |
| Popis: | Cationic lipids are promising non-viral vectors for the cellular delivery of nucleic acids. Important considerations for the development of new delivery vectors are enhanced uptake efficiency, low toxicity and traceability. Traceable gene transfer systems however typically require the inclusion of a labeled excipient, and highly sensitive imaging instrumentation to detect the presence of the label. Recently, we reported the synthesis and characterization of colored, polyene cationic phospholipidoids composed of a rigid, polyenoic acid of predetermined dimension (C20:5 and C30:9) paired with flexible saturated alkyl chains of varying lengths (12:0, 14:0, 16:0, 18:0, 20:0 carbons). Herein, the potential of these cationic phospholipids as siRNA carriers was evaluated through standard liposomal formulations in combination with a neutral helper lipid DOPE. The polyene-based lipids were compared with a standard cationic lipid for siRNA-delivery into luciferase expressing HR5-CL11 cells. Within the series of lipids screened, knockdown results indicated that polyene cationic phospholipids paired with longer saturated alkyl chains are more effective as gene transfer agents, and perform comparably with the commercial lipid EPC. Furthermore, the chromophore associated with the polyene chain allowed tracking of the siRNA delivery using direct observation. The polyene lipoplexes were tracked on both a macroscopic and microscopic level either as a single-component or as a multi-component lipoplex formulation. When combined with a reference EPC, effective knockdown and tracking abilities were combined in a single preparation. |
| Databáze: | OpenAIRE |
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