Shi Qin, Wang Huijie, Tran Covi, Qiu Xingping, Winnik Françoise M, Zhang Xiaoling, Dai Kerong, Benderdour Mohamed, Fernandes Julio C
Orthopaedics Research Laboratory, Research Centre, Sacré-Coeur Hospital, University of Montreal, 5400 West Gouin Boulevard, Montreal, QC, Canada.
J Biomed Biotechnol. 2011;2011:148763. doi: 10.1155/2011/148763. Epub 2010 Dec 28.
50 kDa chitosan was conjugated with folate, a specific tissue-targeting ligand. Nanoparticles such as chitosan-DNA and folate-chitosan-DNA were prepared by coacervation process. The hydrodynamic intravenous injection of nanoparticles was performed in the right posterior paw in normal and arthritic rats. Our results demonstrated that the fluorescence intensity of DsRed detected was 5 to 12 times more in the right soleus muscle and in the right gastro muscle than other tissue sections. β-galactosidase gene expression with X-gal substrate and folate-chitosan-plasmid nanoparticles showed best coloration in the soleus muscle. Treated arthritic animals also showed a significant decrease in paw swelling and IL-1β and PGE₂ concentration in serum compared to untreated rats. This study demonstrated that a nonviral gene therapeutic approach using hydrodynamic delivery could help transfect more efficiently folate-chitosan-DNA nanoparticles in vitro/in vivo and could decrease inflammation in arthritic rats.
50千道尔顿的壳聚糖与叶酸（一种特异性组织靶向配体）偶联。通过凝聚法制备了壳聚糖-DNA和叶酸-壳聚糖-DNA等纳米颗粒。在正常大鼠和关节炎大鼠的右后爪进行纳米颗粒的流体动力学静脉注射。我们的结果表明，在右比目鱼肌和右腓肠肌中检测到的DsRed荧光强度比其他组织切片高5至12倍。用X-gal底物和叶酸-壳聚糖-质粒纳米颗粒检测β-半乳糖苷酶基因表达时，比目鱼肌中染色效果最佳。与未治疗的大鼠相比，接受治疗的关节炎动物的爪肿胀以及血清中IL-1β和PGE₂浓度也显著降低。这项研究表明，使用流体动力学递送的非病毒基因治疗方法有助于在体外/体内更有效地转染叶酸-壳聚糖-DNA纳米颗粒，并可减轻关节炎大鼠的炎症。
