Tailoring new gene delivery designs for specific targets.
Advancing biotechnology spurs the development of new pharmaceutically engineered gene delivery vehicles with the capability to target specific cell types. The low density lipoprotein (LDL) element of the terplex gene carrier is shown to be efficient in delivery to smooth muscle cells as well as inducing minimal toxicity to A7R5 cells in culture. The terplex system condensed plasmid DNA into polyplex sizes ranging from 100 to 400 nm. Terplex demonstrated higher transfection efficacy than Lipofectin. Lactose was conjugated through a poly(ethyl glycol) (PEG) spacer to poly(L-lysine) (PLL) to tailor a gene carrier capable of condensing plasmid DNA. This cationic polymer targeted Hep G2 cells preferentially in culture. The inclusion of a lactose targeting moiety greatly increased the efficacy of the gene carrier over PEG-PLL and Lipofectin. A biodegradable nanoparticle gene carrier, polysaccharide-graft-PLL and poly(D,L-lactic acid), was synthesized and characterized. The nanoparticle size was controllable by changing the copolymer concentration, where the particles could be as small as 60 nm. When polysaccharide was used in the copolymer, the nanoparticle became more DNA adsorbent. The JLI mAb was linked to PLL. This gene carrier targets the antigen confined to stage II immature cortical thymocytes for leukemia therapy. A 20,000 mw PLL backbone was sufficient for compaction of DNA. Folic acid linked to PLL through a PEG spacer is currently being studied for DNA condensation and delivery to membrane associated folate binding protein positive endothelial cancer cells.
Benns
J M
JM
Department of Pharmaceutics and Pharmaceutical Chemistry, Center for Controlled Chemical Delivery, University of Utah, Salt Lake City 84112, USA.
Kim
S W
SW
D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D018390:Gene Targeting / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D013678:Technology, Pharmaceutical; D014162:Transfection