Gene delivery system of pDNA using the blood glycoprotein fetuin.
Yukinobu KodamaHiroki HanamuraTakahiro MuroHiroo NakagawaTomoaki KurosakiTadahiro NakamuraTakashi KitaharaShigeru KawakamiMikiro NakashimaHitoshi SasakiPublished in: Journal of drug targeting (2017)
Fetuin is a biocompatible plasma protein and strongly enhances phagocytosis of bacteria, DNA and apoptotic cells by peripheral blood cells such as monocytes, macrophages and dendritic cells. We developed a novel gene delivery system: ternary complexes constructed with pDNA, polyethylenimine (PEI) and fetuin. Without covalent binding, fetuin was able to coat pDNA-PEI complexes, and stable anionic nanoparticles formed at a weight ratio greater than 30. Optimised pDNA-PEI-fetuin complexes significantly decreased the cytotoxicity of pDNA-PEI complexes in the melanoma cell line B16F10. Furthermore, the pDNA-PEI-fetuin complexes had higher transgene efficiency compared to that of commercial lipofectin previously reported in B16F10 cells despite an anionic surface. The pDNA-PEI-fetuin complexes did not agglutinate with erythrocytes. The pDNA-PEI-fetuin complexes had high gene expression in the spleen after intravenous administration in mice. Thus, the pDNA-PEI-fetuin complexes were a useful in vivo gene delivery system with tropism for the spleen.
Keyphrases
- induced apoptosis
- dendritic cells
- gene expression
- peripheral blood
- cell cycle arrest
- immune response
- dna methylation
- endoplasmic reticulum stress
- physical activity
- low dose
- body mass index
- insulin resistance
- weight loss
- oxidative stress
- small molecule
- metabolic syndrome
- ionic liquid
- cell proliferation
- cell free
- pi k akt
- circulating tumor