College of Pharmacy, Seoul National University, Sinlim-dong, Gwanak-gu, Seoul, South Korea.
J Control Release. 2010 Jul 14;145(2):159-64. doi: 10.1016/j.jconrel.2010.04.005. Epub 2010 Apr 10.
For delivery of siRNA, chitosan (CS) was derivatized with poly-l-arginine (PLR) and polyethylene glycol (PEG). The formation of polyplexes with siRNA was confirmed by gel retardation. The PLR-grafted CS formed nanosized particles with siRNA. PLR-grafted CS showed higher cellular delivery efficiency of siRNA than did CS, pegylated CS, PLR, or pegylated PLR. The extent of reduction in the expression of fluorescent proteins was highest following treatment of the cells using PLR derivatives of CS in complexes with specific siRNAs. Cell viability was greater in populations treated with pegylated CS-PLR than in those treated with PLR. Hemolysis of erythrocytes was reduced upon conjugation of PLR with CS. The delivery of siRNAs via pegylated CS-PLR revealed little dependence on serum. Molecular imaging techniques revealed that the intratumoral administration of red fluorescent protein-specific siRNA in complexes with pegylated CS-PLR significantly silenced the expression of red fluorescent proteins in tumor tissues in vivo. These results indicate that pegylated CS-PLR might be useful for in vivo delivery of therapeutic siRNAs.
为了递送 siRNA，壳聚糖（CS）被聚精氨酸（PLR）和聚乙二醇（PEG）衍生化。通过凝胶阻滞实验证实了 siRNA 与聚电解质复合物的形成。PLR 接枝 CS 与 siRNA 形成纳米颗粒。PLR 接枝 CS 比 CS、PEG 化 CS、PLR 或 PEG 化 PLR 具有更高的 siRNA 细胞递送效率。在用 CS 的 PLR 衍生物与特定 siRNA 形成的复合物处理细胞后，荧光蛋白表达的减少程度最高。用 PEG 化 CS-PLR 处理的细胞群体的细胞活力大于用 PLR 处理的细胞群体。PLR 与 CS 缀合可降低红细胞溶血。通过 PEG 化 CS-PLR 递送 siRNA 几乎不依赖于血清。分子成像技术显示，在复合物中体内给予红色荧光蛋白特异性 siRNA 的多柔比星 CS-PLR 可显著沉默体内肿瘤组织中红色荧光蛋白的表达。这些结果表明，PEG 化 CS-PLR 可能对治疗性 siRNA 的体内递送有用。
