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PEG conjugated VEGF siRNA for anti-angiogenic gene therapy.

Abstract
A novel siRNA delivery system based on polyelectrolyte complex (PEC) micelles was introduced in this study. Vascular endothelial growth factor (VEGF) siRNA was conjugated to poly(ethylene glycol) (PEG) via a disulfide linkage (siRNA-PEG). The siRNA-PEG conjugate could form PEC micelles by interacting with cationic polyethylenimine (PEI) as a core forming agent. The VEGF siRNA-PEG/PEI PEC micelles showed greater stability than naked VEGF siRNA against enzymatic degradation. Under a reductive condition similar to cytosolic environment, an intact form of siRNA was released from the siRNA-PEG conjugate by cleavage of the disulfide linkage. The VEGF siRNA-PEG/PEI PEC micelles effectively silenced VEGF gene expression in prostate carcinoma cells (PC-3) up to 96.5% under an optimized formulation condition. They also showed a far superior VEGF gene silencing effect than VEGF siRNA/PEI complexes even in the presence of serum. This study suggests that the siRNA delivery system using VEGF siRNA-PEG/PEI PEC micelles could be potentially applied to RNAi-based anti-angiogenic treatment of cancer in vivo.
AuthorsSun Hwa Kim, Ji Hoon Jeong, Soo Hyun Lee, Sung Wan Kim, Tae Gwan Park
JournalJournal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 116 Issue 2 Pg. 123-9 (Nov 28 2006) ISSN: 0168-3659 [Print] Netherlands
PMID16831481 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Blood Proteins
  • Disulfides
  • Micelles
  • RNA, Small Interfering
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Polyethylene Glycols
  • Polyethyleneimine
  • monomethoxypolyethylene glycol
  • Glutathione
Topics
  • Blood Proteins (metabolism)
  • Cell Line, Tumor
  • Disulfides (metabolism)
  • Genetic Therapy (methods)
  • Glutathione (metabolism)
  • Humans
  • Male
  • Micelles
  • Neovascularization, Pathologic (metabolism, therapy)
  • Polyethylene Glycols (chemistry)
  • Polyethyleneimine (chemistry)
  • Prostatic Neoplasms (blood supply, metabolism, therapy)
  • RNA Interference
  • RNA Stability
  • RNA, Small Interfering (genetics, metabolism)
  • Time Factors
  • Transfection
  • Vascular Endothelial Growth Factor A (biosynthesis, genetics)

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