Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid

Dual Responsive, Stabilized Nanoparticles for Efficient In Vivo Plasmid Delivery

“…However, the PEG coating negatively affects cellular uptake and intracellular trafficking. [7] Polyplexes that detach the PEG shielding layer in response to signals in the biological microenvironments are an elegant solution to these issues. [8][9][10][11] Biodistribution studies with PEGylated polyplexes have revealed an additional complication: PEGylated polyplexes can exhibit poor stability and premature unpackaging in vivo, likely due to interactions with serum proteins and extracellular matrix components.…”

Efficient Short Interference RNA Delivery to Tumor Cells Using a Combination of Octaarginine, GALA and Tumor-Specific, Cleavable Polyethylene Glycol System

“…PPD and Chol-GALA were synthesized as described previously. 16,18) Dulbecco's modified Eagle medium (DMEM) and fetal bovine serum (FBS) were purchased from Invitrogen (Carlsbad, CA, U.S.A.). Diethyl pyrocarbonate (DEPC)-treated water and G418 were obtained from Nacalai Tesque (Kyoto, Japan).…”

“…16) Therefore, the PEG moiety was removed from the surface of the PPD-modified R8/ GALA-MEND in response to MMP in the culture medium. Then, the R8 of the naked R8/GALA-MEND was able to associate with cell-surface components such as heparane sulfate proteoglycans, 22) which triggered the cellular uptake of R8/GALA-MEND through endocytosis.…”

“…14,15) To overcome this polyethylene glycol (PEG)-associated dilemma, we previously constructed a novel, cleavable, PEG-peptide-DOPE conjugate named PPD, that is cleaved in response to matrix metalloproteinase (MMP), which is specifically secreted from tumor cells. 16) In the present study, we developed an R8/GALA-MEND modified with PPD for siRNA delivery. We first examined the optimal concentration of STR-R8 and Chol-GALA on the lipid envelope to exert sufficient gene silencing, as assessed by in vitro luciferase activity.…”

Nonviral Vectors with a Biosurfactant MEL-A Promote Gene Transfection into Solid Tumors in the Mouse Abdominal Cavity

“…[1][2][3] To develop the efficiency of gene transfection, several nonviral vectors have been investigated. [4][5][6][7] Lipofection using cationic liposomes is noted for its low toxicity and easy preparation. 8,9) In addition, we showed that cationic liposomes with a cholesterol derivative containing a hydrophilic amino head group, cholesteryl-3b-carboxyamidoethylene-Nhydroxyethylamine (OH-Chol) and 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE), achieved high transfection efficiency and low toxicity in vitro.…”