Thermally sensitive cationic polymer nanocapsules for specific cytosolic delivery and efficient gene silencing of siRNA: swelling induced physical disruption of endosome by cold shock.
Pluronic/poly(ethylenimine) (PEI2K) nanocapsules (NCs) exhibiting a thermally reversible swelling/deswelling volume expansion behavior were synthesized and used for an siRNA delivery nanocarrier as well as an effective endosome breaking agent. Pluronic/PEI2K nanocapsules were in a collapsed state with an average size of 118.9+/-15.3 nm at 37 degrees C, but in a swollen state with that of 412.3+/-83.2 nm at 15 degrees C. The collapsed Pluronic/PEI2K NCs having a highly positive surface zeta potential value were utilized to load siRNA-PEG conjugate on the surface via electrostatic interactions. The siRNA-PEG/NCs nanocomplexes were transfected to the cells at 37 degrees C for efficient cellular uptake. The transfected cells were treated with a brief cold shock to induce an abrupt volume expansion of the NCs within an endosome compartment to physically burst out the endosomal membrane. Far efficient gene silencing effects for both green fluorescent protein (GFP) and vascular endothelial growth factor (VEGF) were observed after the cold shock treatment to the transfected cells.
Lee
Soo Hyeon
SH
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, South Korea.
Choi
Seung Ho
SH
Kim
Sun Hwa
SH
Park
Tae Gwan
TG
D002412:Cations; D002470:Cell Survival / Q000187:drug effects; D003080:Cold Temperature; D003600:Cytosol / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D011992:Endosomes / Q000737:chemistry* / Q000648:ultrastructure; D020868:Gene Silencing / Q000187:drug effects*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007097:Imines / Q000009:adverse effects / Q000737:chemistry; D053769:Nanocapsules / Q000009:adverse effects / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry; D011095:Polyethylenes / Q000009:adverse effects / Q000737:chemistry; D011108:Polymers / Q000009:adverse effects / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D014162:Transfection; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D002412:Cations; D007097:Imines; D053769:Nanocapsules; D011095:Polyethylenes; D011108:Polymers; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C505405:poly(ethylene imine); D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols