Folate-linked lipid-based nanoparticles deliver a NFkappaB decoy into activated murine macrophage-like RAW264.7 cells.
Activated macrophages are the key effector cells in rheumatoid arthritis (RA) and secrete multiple mediators of inflammation including proinflammatory cytokines. We investigated delivery of a nuclear factor kappa B (NFkappaB) decoy by folate-linked lipid-based nanoparticles (NP-F) into murine macrophages. The expression of folate receptor (FR) in RAW264.7 cells activated by lipopolysaccaride was confirmed by strong expression of FR mRNA, and association of FITC-labeled folate-BSA conjugate. When transfected via NP-F, the NFkappaB decoy was strongly detected in the cytoplasm, and an inhibitory effect on the translocation of NFkappaB into the nucleus was observed at 0.03 microM of the decoy, suggesting that NP-F effectively delivered the NFkappaB decoy into the cytoplasm. This information is of value for the design of NFkappaB decoy carrier systems targeting FR in activated macrophages in gene therapy for autoimmune diseases such as RA.
Hattori
Yoshiyuki
Y
Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
Sakaguchi
Makoto
M
Maitani
Yoshie
Y
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005492:Folic Acid; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000493:pharmacokinetics* / Q000494:pharmacology; D049329:Nanostructures; D014162:Transfection / Q000379:methods
D016328:NF-kappa B; D005492:Folic Acid