TY - JOUR
T1 - Smart DNA Vectors based on cyclodextrin polymers
T2 - Compaction and endosomal release
AU - Wintgens, Véronique
AU - Leborgne, Christian
AU - Baconnais, Sonia
AU - Burckbuchler, Virginie
AU - Le Cam, Eric
AU - Scherman, Daniel
AU - Kichler, Antoine
AU - Amiel, Catherine
PY - 2012/2/1
Y1 - 2012/2/1
N2 - Purpose: Neutral β-cyclodextrin polymers (polyβCD) associated with cationic adamantyl derivatives (Ada) can be used to deliver plasmid DNA into cells. In absence of an endosomolytic agent, transfection efficiency remains low because most complexes are trapped in the endosomal compartment. We asked whether addition of an imidazole-modified Ada can increase efficiency of polyβCD/cationic Ada-based delivery system. Methods We synthesized two adamantyl derivatives: Ada5, which has a spacer arm between the Ada moiety and a bi-cationic polar head group, and Ada6, which presents an imidazole group. Strength of association between polyβCD and Ada derivatives was evaluated by fluorimetric titration. Results Gel mobility shift assay, zeta potential, and dark field transmission electron microscopy experiments demonstrated the system allowed for efficient DNA compaction. In vitro transfection experiments performed on HepG2 and HEK293 cells revealed the quaternary system polyβCD/Ada5/Ada6/DNA has efficiency comparable to cationic lipid DOTAP. Conclusion We successfully designed fine-tuned DNA vectors based on cyclodextrin polymers combined with two new adamantyl derivatives, leading to significant transfection associated with low toxicity.
AB - Purpose: Neutral β-cyclodextrin polymers (polyβCD) associated with cationic adamantyl derivatives (Ada) can be used to deliver plasmid DNA into cells. In absence of an endosomolytic agent, transfection efficiency remains low because most complexes are trapped in the endosomal compartment. We asked whether addition of an imidazole-modified Ada can increase efficiency of polyβCD/cationic Ada-based delivery system. Methods We synthesized two adamantyl derivatives: Ada5, which has a spacer arm between the Ada moiety and a bi-cationic polar head group, and Ada6, which presents an imidazole group. Strength of association between polyβCD and Ada derivatives was evaluated by fluorimetric titration. Results Gel mobility shift assay, zeta potential, and dark field transmission electron microscopy experiments demonstrated the system allowed for efficient DNA compaction. In vitro transfection experiments performed on HepG2 and HEK293 cells revealed the quaternary system polyβCD/Ada5/Ada6/DNA has efficiency comparable to cationic lipid DOTAP. Conclusion We successfully designed fine-tuned DNA vectors based on cyclodextrin polymers combined with two new adamantyl derivatives, leading to significant transfection associated with low toxicity.
KW - Cyclodextrin
KW - Electron microscopy
KW - Gene transfer
KW - Inclusion chemistry
KW - Proton sponge
UR - http://www.scopus.com/inward/record.url?scp=84860880044&partnerID=8YFLogxK
U2 - 10.1007/s11095-011-0560-0
DO - 10.1007/s11095-011-0560-0
M3 - Article
C2 - 21847694
AN - SCOPUS:84860880044
SN - 0724-8741
VL - 29
SP - 384
EP - 396
JO - Pharmaceutical research
JF - Pharmaceutical research
IS - 2
ER -