COATSOME® SS-series New
SS-cleavable and pH-responsive lipid-like material for gene delivery and nucleic acid delivery system.
We developed COATSOME®SS-series for gene delivery and nucleic acid delivery system. COATSOME®SS-series mounts dual sensing motifs that can respond to the intracellular environment; tertiary amines responsive to an acidic compartment (endosome/lysosome) for membrane destabilization, and disuifide bonding that can be cleaved in reductive environment (cytosol).
Proof of concept:
1) Particle formation
2) Serum resistance
3) Membrane disruption in the cells
The particle composed COAT-SOME® SS-series is stable in serum, hence enzymatic de-gradation of pDNA was prevented by encapsulation. Also the particle composed of COATSOME® SS-series was effectively destabilized in the cytoplasmic environment.
*H. Akita et al., Adv. Healthcare Mater., 2, 1120-1125 (2013)
Example of use
1) For in vitro gene delivery
SS-20/3AP-04 has vitamin A moiety as hydrophobic chains. Particle composed SS-20/3AP-04 showed 15-fold higher gene expression than that of SS-14/3AP-01 which hydrophobic chain is myristic acid moiety. Cells were transfected with particles containing 1.6 mg rhodamine-labeled pDNA (red). Nucleus and endosome/lysosome were stained with Hoechst33342 (blue) and LysoTracker® green DND-26 (green). Scale bars indicate 20mm.
T.Tanaka et al., Biomaterials., 35, 1755-1761 (2014)
2) For Hepatic gene delivery
The particle composed SS-14/3AP-01 is suitable for hepatic gene delivery. Using SS-14/3AP-01, gene expression was retained for 2 weeks.
M.Ukawa et al., Adv. Healthcare Mater., 3, 1222-1229 (2014)
3) For tumor gene delivery
The particle composed SS-33/3AP-05 encapsulating pDNAencoding sFlt-1 respond to treatment of subcutaneously implanted OS-RC-2 tumor in mice.
H.Akita et al., J.Controlled Release, 2014, DOI: 10.1016/j.jconrel.2014.12.029
4) For hepatic siRNA delivery
SS-33/4PE-15 is designed to achieve efficient endosomal escape by adjusting liposomal pKa. The particle composed of SS-33/4PE-15 encapsulating siRNA showed efficient silencing of gene expression in vivo.
Preparation of particles for siRNA delivery: A lipid solution in t-BuOH was prepared by mixing cholesterol, PEGylated lipid and COATSOME®SS-series to achieve 18mM total lipid. While stirring the lipid solution, A siRNA solution in 20 mM Malate buffer (pH 4.0, 30 mM NaCl) was quickly added, and thereafter 20 mM Malate buffer (pH 4.0, 30 mM NaCl) was added to dilute the mixture. The mixture was concentrated by ultrafiltration. Thereafter, it was diluted with PBS (pH 7.4), and again concentrated. Finally, it was diluted with PBS to 0.05 μg/μL lipid concentration.