Biscarbamate cross-linked low molecular weight PEI for delivering IL-1 receptor antagonist gene to synoviocytes for arthritis therapy.
Cytoxicity is an essential concern for polyethyleneimine 25 kDa (PEI 25 kDa), a widely reported, highly effective transfection agent used in gene delivery. In our recent experiments, Small molecular weight cross-linked poly(ethylene imine) by biscarbamate linkage (PEI-Bu) (Mn: 3278, Mw: 4289) can reduce target cell apoptosis induced by polycationic transfection, and has almost the same DNA condensation capability as PEI 25 kDa. PEI-Bu showed significantly higher activity and lower cytotoxicity than PEI 25 kDa in transfecting the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) gene to rat synoviocytes, an optimal target for arthritis treatment. The expression of IL-1Ra in synoviocytes then suppresses the expression of metalloproteases 13 (MMP13) gene, which is responsible for cartilage destruction regulated by IL-1β in arthritis. In conclusion, PEI-Bu is a promising tool for delivering IL-1Ra gene to synoviocytes for arthritis therapy.
The Key Laboratory of Stem Cell Biology, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, PR China.
Shengnan
S
Xiang
Jing
J
Su
Haijun
H
Tong
Fei
F
Yang
Wenxue
W
Tong
Weien
W
Yuan
Fei
F
Wu
Chuandong
C
Wang
Tuo
T
Jin
Kerong
K
Dai
Xiaoling
X
Zhang
D000818:Animals; D001168:Arthritis / Q000473:pathology / Q000628:therapy*; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry*; D016923:Cell Death; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000737:chemistry*; D016503:Drug Delivery Systems; D004587:Electrophoresis, Agar Gel; D015316:Genetic Therapy; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics* / Q000627:therapeutic use*; D042541:Intracellular Space / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D053078:Membrane Potential, Mitochondrial; D018613:Microscopy, Confocal; D010957:Plasmids / Q000378:metabolism; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared; D013583:Synovial Membrane / Q000473:pathology*; D014162:Transfection
D002219:Carbamates; D003432:Cross-Linking Reagents; D053590:Interleukin 1 Receptor Antagonist Protein; D011094:Polyethyleneimine