NOF Group
SS-cleavable and pH-responsive lipid like material (COATSOME® SS-Series) !NEW!
SS-cleavable and pH-responsive Lipid Like Material (COATSOME® SS-Series)
COATSOME® SS-series New
SS-cleavable and pH-responsive lipid-like material for gene delivery and nucleic acid delivery system
We have developed COATSOME® SS-series lipids for effective intracellular delivery and lower toxicity. COATSOME® SS-series contains dual sensing motifs that can respond to the intracellular environment; tertiary amines respond to an acidic compartment (endosome/lysosome) for membrane destabilization, and disulfide bond that can cleave in reductive environment (cytoplasm). These two units synergize for efficient intracellular delivery of encapsulated drugs with enhanced biosafety.
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• Proof of concept
Particle formation
Serum resistance
Particle disruption in the cytoplasm
Using the non-cleavable lipid as a component of membrane, pDNA dominantly colocalizes with lipid membrane. In contrast, using SS-Cleavable lipid instead of the non-cleavable lipid, the pDNA does not colocalize with membrane and can be found prominently. These show that cleavage of the disulfide bonding accelerates particle disruption.
• Toxitity of the particles
Cytotoxicity of the particles
Toxicity of the particles in vivo
In vitro transfection applying non-cleavable lipid shows sharp decline of cell survival rate by increase of the dose concentration. On the other hand, applying SS-Cleavable lipid, high cell survival rate is kept even when the dose is increased up to 10 folds of general transfection condition. Further, in the hepatotoxicity marker, SS-Cleavable lipid clearly shows biological safety in comparison with non-cleavable lipid.