Kim Tae Hee, Nah Jae Woon, Cho Myung-Haing, Park Tae Gwan, Cho Chong Su
School of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Korea.
J Nanosci Nanotechnol. 2006 Sep-Oct;6(9-10):2796-803. doi: 10.1166/jnn.2006.434.
Dendritic cells (DCs) are professional antigen presenting cells that induce, sustain, and regulate immune responses. Gene modification of DCs is of particular interest for immunotherapy of diseases where the immunes system has failed or is abnormally regulated, such as in cancer or autoimmune disease. Gene transfer using non-viral vectors is a promising approach for the safe delivery of therapeutic DNA. Among various non-viral vectors, chitosan is considered to be a good candidate for gene delivery system, however, lack of cell specificity and low transfection of chitosan need to be overcome prior to clinical use. In this study, mannosylated chitosan (MC) was prepared to induce the receptor-mediated endocytosis and targeting into antigen presenting cells (APCs), especially DCs having mannose receptors. MC showed great ability to form complexes with DNA and showed suitable physicochemical properties for gene delivery system. It had low cytotoxicity and exhibited much enhanced gene transfer efficiency on the macrophage cell line than chitosan itself. Also, MC/DNA complex was more efficient for transferring IL-12 gene into DCs rather than water-soluble chitosan (WSC)/DNA one, which resulted in better induction of INF-gamma from DCs. Therefore, MC is a promising gene delivery system for repeated administration to maintain sustained gene expression, thereby opening the possibility for immunotherapy.
树突状细胞（DCs）是专业的抗原呈递细胞，可诱导、维持和调节免疫反应。对于免疫系统功能失效或调节异常的疾病，如癌症或自身免疫性疾病，DCs的基因修饰在免疫治疗中具有特别的意义。使用非病毒载体进行基因转移是安全递送治疗性DNA的一种有前景的方法。在各种非病毒载体中，壳聚糖被认为是基因递送系统的良好候选者，然而，在临床应用之前，壳聚糖缺乏细胞特异性和低转染率的问题需要克服。在本研究中，制备了甘露糖基化壳聚糖（MC）以诱导受体介导的内吞作用并靶向抗原呈递细胞（APC），特别是具有甘露糖受体的DCs。MC显示出与DNA形成复合物的强大能力，并显示出适合基因递送系统的理化性质。它具有低细胞毒性，并且在巨噬细胞系上的基因转移效率比壳聚糖本身有很大提高。此外，MC/DNA复合物将IL-12基因转移到DCs中的效率比水溶性壳聚糖（WSC）/DNA复合物更高，这导致DCs更好地诱导INF-γ。因此，MC是一种有前景的基因递送系统，可重复给药以维持持续的基因表达，从而为免疫治疗开辟了可能性。
