Multifunctional siRNA delivery system: polyelectrolyte complex micelles of six-arm PEG conjugate of siRNA and cell penetrating peptide with crosslinked fusogenic peptide.
For therapeutic applications of small interfering RNA (siRNA), serum stability, enhanced cellular uptake, and facile endosome escape are key issues for designing carriers. In this study, green fluorescent protein (GFP) siRNA was conjugated to a six-arm polyethylene glycol (PEG) derivative via a reducible disulfide linkage (6PEG-siRNA). The 6PEG-siRNA conjugate was also functionalized with a cell penetrating peptide, Hph1 to enhance its cellular uptake property (6PEG-siRNA-Hph1). The 6PEG-siRNA-Hph1 conjugate was electrostatically complexed with cationic self-crosslinked fusogenic KALA peptide (cl-KALA) to form multifunctional polyelectrolyte complex micelles for gene silencing. The resultant siRNA complex formulation with multiple PEG chains showed superior physical stability and resistance to enzymatic degradation. The 6PEG-siRNA-Hph1/cl-KALA complexes exhibited enhanced GFP gene silencing efficiency for MDA-MB-435 cells in the serum containing condition. The current reducible and multifunctional polyelectrolyte complex micelles are expected to have high potential for efficient delivery of therapeutic siRNA.
Choi
Sung Won
SW
Dept. of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea 305-701.
Lee
Soo Hyeon
SH
Mok
Hyejung
H
Park
Tae Gwan
TG
D002352:Carrier Proteins / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D016503:Drug Delivery Systems; D004573:Electrolytes / Q000737:chemistry; D020868:Gene Silencing; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008823:Micelles; D010455:Peptides / Q000737:chemistry*; D063150:Polycomb Repressive Complex 1; D011092:Polyethylene Glycols / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004573:Electrolytes; C105114:KALA amphipathic peptide; D008823:Micelles; C491239:PHC1 protein, human; D010455:Peptides; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D063150:Polycomb Repressive Complex 1