Galactosylated low molecular weight chitosan as DNA carrier for hepatocyte-targeting
Galactosylated low molecular weight chitosan as DNA carrier for hepatocyte-targeting
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DOI：
10.1016/s0378-5173(03)00082-6
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发表时间：
2003-04-14
影响因子：
5.8
通讯作者：
Zhang, JF
中科院分区：
文献类型：
--
作者：
Gao, SY;Chen, JN;Zhang, JF
壳聚糖具有DNA复合的潜力，并且可用作基因递送的非病毒载体。制备了高纯度低分子量壳聚糖（LMWC）。具有半乳糖基团的乳糖酸（LA）与LMWC偶联，用于肝脏特异性。制备了一系列半乳糖化-LMWC（gal-LMWC）样品，涵盖了一系列半乳糖基团含量。采用复凝聚法制备了壳聚糖/DNA复合物。用Gal-LMWCs将pSV-β-半乳糖苷酶报告基因转染人肝癌细胞（HepG 2）。L-02 SMMC-7721和人宫颈腺癌细胞系（HeLa）。采用β-半乳糖苷酶法检测gal-LMWCs的转染效率，并与脂质体、磷酸钙（CaP）进行比较。高分子量壳聚糖（HMWC）和低分子量壳聚糖。Gal-LMWC/DNA复合物对肝细胞显示出非常有效的细胞选择性转染。半乳糖基化程度越高，半乳糖基化低分子量细胞的转染效率越高。用MTT法测定了改性壳聚糖的细胞毒性，结果表明改性壳聚糖具有较低的细胞毒性。证明了修饰的壳聚糖载体具有用作安全的基因递送系统的潜力。(C)2003 Elsevier Science B. V.保留所有权利。
Chitosan has the potential for DNA complexation and is useful as a non-viral vector for gene delivery. Highly purified low molecular weight chitosan (LMWC) was prepared. Lactobionic acid (LA) bearing galactose group as coupled with LMWC for liver-specificity. A series of galactoslated-LMWC (gal-LMWC) samples covering a range of galactose group contents were prepared. The chitosan/DNA complexes were obtained using a complex coacervation process. Gal-LMWCs were used to transfer pSV-beta-galactosidase reporter gene into human hepatocellular carcinoma cell (HepG2). L-02. SMMC-7721, and human cervix adenocarcinoma cell line (HeLa) cell lines in vitro. Transfection efficiency of gal-LMWCs was evaluated by beta-galactosidase assay and compared with those of lipofectin, calcium phosphate (CaP). high molecular weigh chitosan (HMWC) and LMWC. Gal-LMWC/DNA complex shows a very, efficient cell selective transfection to hepatocyte. The transfection efficiency of gal-LMWCs increased with the improvement of the galactosylation degree. Cytotoxicity of gal-LMWC was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltentrazolium bromide (MTT) assay and the results show that the modified chitosan has relatively low cytotoxicity. giving the evidence that the modified chitosan vector has the potential to be used as a safe gene-delivery system. (C) 2003 Elsevier Science B.V. All rights reserved.