基于PAMAM树状大分子的自组装三元基因复合物的制备与表征  

Preparation and Characterization of PAMAM Dendrimer-based Self-assembled Ternary Gene Complexes

作　　者：张璐[1] 程丽芳[1] 程亮[1] 阮园[1] 陈大为[1,2] 

机构地区：[1]苏州大学药学院,江苏苏州215123 [2]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《中国医药工业杂志》2014年第8期739-743,770,共6页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金(81173004;81302719)

摘　　要：以4代聚酰胺-胺(PAMAM)树状大分子为siRNA的载体和具有主动靶向功能的透明质酸(HA)为被膜材料,依次通过静电吸附制备载siRNA的二元自组装基因复合物siRNA/PAMAM和三元自组装基因复合物siRNA/PAMAM/HA。所得siRNA/PAMAM/HA呈类球形。随HA包覆量的增加,复合物粒径增加,ζ电位降低,并均能有效包载并保护siRNA。体外细胞试验表明,HA能显著降低PAMAM对MDA-MB-231乳腺癌细胞的毒性。此外,HA的包覆能增加MDA-MB-231细胞对该复合物的摄取,增强复合物的主动靶向性,且当HA的包覆量为25%(电荷比)时,细胞摄取量最高。Based on the generation 4 poly （amidoamine） （PAMAM） dendrimers, the binary and ternary self- assembled gene complexes, siRNA/PAMAM and siRNA/PAMAM/HA, were prepared by successive electrostatic adsorption of PAMAM with siRNA and hyaluronic acid （HA） for active targeting of siRNA delivery. The prepared siRNA/PAMAM/HA particles were spherical. With the increase of the charge ratio of HA on surface of the ternary complexes, the mean particle size increased and the ~ potential decreased. Moreover, the complexes were able to combine and protect siRNA efficiently. The results showed that the shielding with HA could reduce the toxicity of PAMAM to MDA-MB-231 breast cancer cells significantly. Compared with siRNA/PAMAM complexes without HA coating, the siRNA/PAMAM/HA complexes showed obviously increased uptake and active targeting ability. And the highest cellular uptake was observed when the shielding ratio of HA was 25 % （charge ratio）.

关 键 词：PAMAM树状大分子 小干扰RNA 透明质酸 基因递送 主动靶向 细胞毒性 

分 类 号：R944.9[医药卫生—药剂学]