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Synthesis and characterization of a PAMAM dendrimer nanocarrier functionalized by HA for targeted gene delivery systems and evaluation in vitro
Journal of Biomaterials Science, Polymer Edition ( IF 3.6 ) Pub Date : 2020-10-09 , DOI: 10.1080/09205063.2020.1827921
Haimei Hu 1 , Han Wang 1 , Shuanghong Liang 1 , Xiaoling Li 1 , Dan Wang 1
Affiliation  

Abstract

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 in vitro 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.



中文翻译:

HA 功能化的 PAMAM 树枝状聚合物纳米载体的合成和表征,用于靶向基因递送系统和体外评估

摘要

Poly(amido-amine) (PAMAM)是药物和基因递送领域研究最广泛的树枝状大分子之一,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,可以聚合并被认为是一种非免疫原性聚合物,通过与 CD 44 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HA 修饰的 PAMAM。和PAMAM由具有不同接枝密度(5%、15%、25%)和分子量(HA3850、HA17200)的HA结合。我们研究了复合物的粒径、zeta 电位和琼脂糖凝胶电泳分析。此外,在体外评估了新复合物的细胞毒性、转染效率和转染机制。在 Hela、Bel-7402 和 HepG2 细胞系中转染。结果显示,经HA修饰后,聚合物的细胞毒性有所降低,一些聚合物的尺寸在适当的重量比下也低于200 nm,转染效率也接近于复合物G4 PAMAM/DNA。与未修饰的树枝状化合物相比,PAMAM G4-HA3850-5%和PAMAM G5-HA3850-5%的DNA递送能力在癌细胞系中有所提高。它是用于靶向基因递送的潜在候选者。

更新日期:2020-10-09
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