4.8 Article

Biscarbamate cross-linked low molecular weight PEI for delivering IL-1 receptor antagonist gene to synoviocytes for arthritis therapy

期刊

BIOMATERIALS
卷 33, 期 27, 页码 6520-6532

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.05.044

关键词

Cross-linking; Nanoparticle; Arthritis; Gene transfer

资金

  1. The Ministry of Science and Technology of China [2011DFA30790, 2010CB945600]
  2. National Natural Science Foundation of China [81190133, 81001416]
  3. Chinese Academy of Sciences [XDA01030404, KSCX2-EW-Q-1-07]
  4. Science and Technology Commission of Shanghai Municipality [11QH1401600]
  5. Shanghai Municipal Education Commission [J50206, 10SG22]
  6. Shanghai Jiao Tong University [YG2010MS48]

向作者/读者索取更多资源

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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