Multifunctional nanoparticles for gene delivery and spinal cord injury

Multifunctional nanoparticles for gene delivery and spinal cord injury
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DOI:
10.1002/jbm.a.35489
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发表时间:
2015-11-01
影响因子:
4.9
通讯作者:
Ha, Yoon
Ha, Yoon
中科院分区:
工程技术3区
文献类型:
--
作者:
Gwak, So-Jung;Koo, Heebeom;Ha, Yoon

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甲基强的松龙(MP)是一种糖皮质激素,用于治疗脊髓损伤(SCI)。以低分子量壳聚糖为原料,制备壳聚糖-MP偶联物,研究MP的基因治疗、抗炎和抗凋亡作用。MTT法和荧光素酶法检测壳聚糖-MP纳米粒的细胞毒性和质粒DNA的转染效率。将壳聚糖-MP/pDNA复合物注射到损伤的脊髓中,分别使用末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)和ED 1染色来评价这些复合物的抗炎和抗凋亡作用。此外,为了评估壳聚糖-MP/pDNA复合物的分布,将包封的p-gal壳聚糖-MP注射到注射部位。在用壳聚糖-MP缀合物处理的细胞和未处理的细胞中,细胞存活率相似。用壳聚糖-MP/pDNA处理的细胞中的荧光素酶表达高于用壳聚糖/pDNA处理的细胞。壳聚糖-MP/pDNA复合物还减少损伤部位的细胞凋亡和炎症。这些结果表明,壳聚糖-MP缀合物是治疗SCI的有效基因递送系统。(c)2015 Wiley Periodicals,Inc. J Biomed Mater Res Part A:103A:3474-3482,2015.
Methylprednisolone (MP) is a glucocorticoid that is used as an anti-inflammatory agent to the treat spinal cord injury (SCI). A low molecular weight chitosan was used to synthesize chitosan-MP conjugate, which was used to evaluate the gene therapy, anti-inflammatory and anti-apoptotic effects of MP. The cytotoxicity of chitosan-MP nanoparticles and the transfection efficiency of plasmid DNA were evaluated by MTT and luciferase assays. A chitosan-MP/pDNA complexes was injected into injured spinal cord to evaluate the anti-inflammatory and anti-apoptotic effects of these complexes using terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL) and ED1 staining, respectively. In addition, to evaluate the distribution of chitosan-MP/pDNA complexes, p-gal encapsulated chitosan-MP was injected into the injected site. Cell survival was similar in cells treated with chitosan-MP conjugate and untreated cells. Luciferase expression was higher in cells treated with the chitosan-MP/pDNA than cells treated with the chitosan/pDNA. The chitosan-MP/pDNA complexes also reduced apoptosis and inflammation at the injury site. These results suggest that chitosan-MP conjugation is an effective gene delivery system to treat SCI. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3474-3482, 2015.