pH-Responsive Nanometric Polydiacetylenic Micelles Allow for Efficient Intracellular siRNA Delivery.
A novel generation of pH-responsive photopolymerized diacetylenic amphiphile (PDA) micelles with a diameter of 10 nm was designed and optimized for the intracellular delivery of siRNAs. Dialysis and photopolymerization of the micelles allowed a strong reduction of the cytotoxicity of the nanovector, while the hydrophilic histidine headgroup permitted enhancing the siRNA delivery potential by improving the endosomal escape via imidazole protonation. These PDA-micellar systems were fully characterized by DLS, TEM, and DOSY-NMR experiments. The resulting bioactive complexes of PDA-micelles with siRNA were shown to have an optimal size below 100 nm.
Manon
M
Ripoll
Patrick
P
Neuberg
Antoine
A
Kichler
Laboratory of Therapeutic Innovation, UMR7200 CNRS-Université de Strasbourg, Faculté de Pharmacie , Illkirch 67401, France.
Nassera
N
Tounsi
Alain
A
Wagner
Jean-Serge
JS
Remy
D016503:Drug Delivery Systems; D011992:Endosomes; D006639:Histidine; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D011108:Polymers; D034741:RNA, Small Interfering
D008823:Micelles; D011108:Polymers; D034741:RNA, Small Interfering; D006639:Histidine
imidazole; micelles; photopolymerization; proton sponge effect; siRNA