S-Space College of Veterinary Medicine (수의과대학) Dept. of Veterinary Medicine (수의학과) Journal Papers (저널논문_수의학과)
Targeted Gene Delivery via N-Acetylglucosamine Receptor Mediated Endocytosis
- Singh, Bijay; Maharjan, Sushila; Kim, You-Kyoung; Jiang, Tao; Islam, Mohammad Ariful; Kang, Sang-Kee; Cho, Myung-Haing; Choi, Yun-Jaie; Cho, Chong-Su
- Issue Date
- Journal of Nanoscience and Nanotechnology, Vol.14 No.11, pp.8356-8364
- Receptor-mediated endocytosis is a promising approach of gene delivery into the target cells via receptor ligand interaction. Vimentins at the cell surface are recently known to bind N-acetylglucosamine (GIcNAc) residue, therefore, the cell surfaces of vimentin-expressing cells could be targeted by using the GIcNAc residue as a specific ligand for receptor-mediated gene delivery. Here, we have developed polymeric gene delivery vectors, based on poly(ethylene oxide)(PEO) and poly(aspartamide), namely poly[(aspartamide)(diethylenetriamine)]-b[PEO-(GIcNAc)] (PADPG) and poly[(aspartamide)(diethylenetriamine)]-b-[PEO] (PADP) to elucidate the efficiency of GIcNAc ligand for gene delivery through receptor mediated endocytosis. To determine the efficiency of these polymeric vectors for specific gene delivery, the DNA condensation ability of PADPG and PADP and the subsequent formation of polymeric nanoparticles were confirmed by gel retardation assay and transmission electron microscopy respectively. Both PADPG and PADP had lower cytotoxicity than polyethylenimine 25 K (PEI 25 K). However, their transfection efficiency was comparatively lower than PEI 25 K due to hydrophilic property of PEO in the vectors. To observe the stability of polymeric nanoparticles, the transfection of PADPG and PADP was carried out in the presence of serum. Favorably, the interfering effect of serum on the transfection efficiency of PADPG and PADP was also very low. Finally, when the cell specificity of these polymeric vectors was investigated, PADPG had high gene transfection in vimentin-expressing cells than vimentin-deficiency cells. The high transfection efficiency of PADPG was attributed to the GIcNAc in the polymeric vector which interact specifically with vimentin in the cells for the receptor-mediated endocytosis. The competitive inhibition assay further proved the receptor-mediated endocytosis of PADPG. Thus, this study demonstrates that conjugation of GIcNAc is an effective and rational way to prepare a suitable vector for targeted gene delivery to vimentin-expressing cells.
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