School of life sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
J Biomater Sci Polym Ed. 2021 Feb;32(2):205-228. doi: 10.1080/09205063.2020.1827921. Epub 2020 Oct 9.
Poly(amido-amine) (PAMAM), one of the most widely studied dendrimers in the field of drug and gene delivery, can enhance the stability of DNA and deliver it to cell cytosol; hyaluronic acid (HA), a simple disaccharide unit, can polymerize and is considered a polymer of non-immunogenicity, which has an intrinsic targeting property for many cancer cells by interacting with CD 44. In this study, we had synthesized and characterized a series of PAMAM modified by HA. and PAMAM was conjugated by HA with different grafting density (5%, 15%, 25%) and molecular weight (HA3850, HA17200). We had investigated the particle size, zeta potential and Agarose gel electrophoresis assays of polyplexes. Besides, the cytotoxicity, transfection efficiency and the mechanisms of transfection of new polyplexes were assessed following transfection in Hela, Bel-7402 and HepG2 cells lines. In the results, modified by HA, the cytotoxicity of polymer had reduced and the size of some polymers also below 200 nm in appropriate weight ratio, and transfection efficiency had also close to the polyplexes G4 PAMAM/DNA were observed. Compared with the unmodified dendrimers compounds, the DNA delivering capacity of PAMAM G4-HA3850-5% and PAMAM G5-HA3850-5% had improved in cancer cells line. It is a potential candidate used for targeted gene delivery.
聚（酰胺-胺）（PAMAM）是药物和基因传递领域研究最多的树状大分子之一，它可以增强 DNA 的稳定性并将其递送至细胞质；透明质酸（HA）是一种简单的二糖单元，可聚合且被认为是非免疫原性的聚合物，通过与 CD44 相互作用，对许多癌细胞具有内在的靶向特性。在本研究中，我们合成并表征了一系列经 HA 修饰的 PAMAM。并且，PAMAM 通过 HA 与不同的接枝密度（5%、15%、25%）和分子量（HA3850、HA17200）进行了连接。我们研究了聚集体的粒径、Zeta 电位和琼脂糖凝胶电泳分析。此外，在 Hela、Bel-7402 和 HepG2 细胞系中转染后，评估了新的聚集体的细胞毒性、转染效率和转染机制。结果表明，经 HA 修饰后，聚合物的细胞毒性降低，某些聚合物的粒径也在适当的重量比下降至 200nm 以下，并且转染效率也接近 G4 PAMAM/DNA 聚集体。与未修饰的树状大分子化合物相比，PAMAM G4-HA3850-5%和 PAMAM G5-HA3850-5%在癌细胞系中的 DNA 递送能力得到了提高。它是一种用于靶向基因传递的潜在候选物。
