Journal
BIOMATERIALS
Volume 33, Issue 27, Pages 6520-6532Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.05.044
Keywords
Cross-linking; Nanoparticle; Arthritis; Gene transfer
Funding
- The Ministry of Science and Technology of China [2011DFA30790, 2010CB945600]
- National Natural Science Foundation of China [81190133, 81001416]
- Chinese Academy of Sciences [XDA01030404, KSCX2-EW-Q-1-07]
- Science and Technology Commission of Shanghai Municipality [11QH1401600]
- Shanghai Municipal Education Commission [J50206, 10SG22]
- Shanghai Jiao Tong University [YG2010MS48]
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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-1 beta in arthritis. In conclusion, PEI-Bu is a promising tool for delivering IL-1Ra gene to synoviocytes for arthritis therapy. (c) 2012 Elsevier Ltd. All rights reserved.
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