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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。
Four generations of polyamidoamine (PAMAM) dendrimer as siRNA carrier and active targeting hyaluronic acid (HA) as coating material were prepared by electrostatic adsorption in order to carry siRNA-based binary self-assembly gene complex siRNA / PAMAM and ternary self-assembly gene complexes siRNA / PAMAM / HA. The resulting siRNA / PAMAM / HA was spheroidal. With the increase of the amount of HA coating, the composite particle size increased, the zeta potential decreased, and can effectively contain and protect the siRNA. In vitro cell tests show that HA can significantly reduce the toxicity of PAMAM to MDA-MB-231 breast cancer cells. In addition, HA encapsulation increased uptake of this complex by MDA-MB-231 cells and enhanced the active targeting of the complex, with the highest cellular uptake when the HA coating amount was 25% (charge ratio) .