Biomaterial Database

Use of poly(ethylene glycol)-lipid conjugates to regulate the surface attributes and transfection activity of lipid-DNA particles. 2000

P Harvie, and F M Wong, and M B Bally

Department of Advanced Therapeutics, British Columbia Cancer Agency, 601 West 10th Ave., Vancouver, B.C., V5Z 1L3, Canada.

We evaluated the use of poly(ethylene glycol) (PEG)-modified lipids to control the surface properties of a lipid-based gene transfer system. The lipid-DNA particles (LDPs) used form spontaneously when plasmid DNA is added to mixed detergent lipid micelles consisting of the non-ionic detergent n-octyl-D-glucopyranoside, the cationic lipid dioleyldimethylammonium chloride (DODAC), the zwitterionic lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and selected PEG-modified phosphatidylethanolamines. The inclusion of DODAC is required to form the hydrophobic lipid-DNA complex. DOPE is included to facilitate dissociation of DNA from the cationic lipid and the PEG-modified lipids are added in an effort to stabilize the surface attributes of the resulting lipid-DNA particles. We used PEG-lipids that varied in acyl chain composition because of recent results demonstrating acyl chain dependent transfer of PEG-lipids from lipid vesicles, providing the potential to allow a transformation of the surface properties due to loss of surface grafted PEG. The addition of PEG-modified lipids does not interfere in LDP formation and its presence favors formation of smaller particles (75 nm in contrast to 130 nm in the absence of the PEG-modified lipid). PEG-lipid incorporation causes a concentration dependent reduction in LDP-mediated transfection of B16/BL6 melanoma cells, a result that can be partially attributed to a reduction in particle binding to cells. However, significant LDP binding to B16/BL6 cells was still observed under conditions where LDP transfection activity was reduced by more than 85%. The potential for PEG to interfere with LDP processing following cell binding is discussed.

UI	MeSH Term	Description	Entries
D008055	Lipids	A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)	Lipid
D008546	Melanoma, Experimental	Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.	B16 Melanoma,Melanoma, B16,Melanoma, Cloudman S91,Melanoma, Harding-Passey,Experimental Melanoma,Experimental Melanomas,Harding Passey Melanoma,Melanomas, Experimental,B16 Melanomas,Cloudman S91 Melanoma,Harding-Passey Melanoma,Melanoma, Harding Passey,Melanomas, B16,S91 Melanoma, Cloudman
D010316	Particle Size	Relating to the size of solids.	Particle Sizes,Size, Particle,Sizes, Particle
D011092	Polyethylene Glycols	Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS.	Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005822	Genetic Vectors	DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.	Cloning Vectors,Shuttle Vectors,Vectors, Genetic,Cloning Vector,Genetic Vector,Shuttle Vector,Vector, Cloning,Vector, Genetic,Vector, Shuttle,Vectors, Cloning,Vectors, Shuttle
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013499	Surface Properties	Characteristics or attributes of the outer boundaries of objects, including molecules.	Properties, Surface,Property, Surface,Surface Property
D014162	Transfection	The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.	Transfections
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured