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基于肿瘤微环境pH-redox智能响应多功能纳米靶向载体的制备及表征

Preparation and characterization of multi-functional targeting nano-carrier based on pH-redox tumor microenvironment

  • 摘要: 利用透明质酸有效靶向肿瘤细胞CD44受体的功能,在寡聚透明质酸的结构基础上,引入对pH敏感的缩酮键和对还原环境敏感的二硫键,构建一种新型基于肿瘤微环境的pH-redox智能响应多功能纳米靶向载体——两亲性寡聚透明质酸-巯基薄荷缩酮(oHMST),利用1H NMR、IR和 ESI-MS技术对其结构进行表征确证。通过透析法制备了载姜黄素胶束,并初步考察了制剂的粒径、电位、电镜形貌特征以及 pH、还原敏感特性。结果表明,成功合成了两亲性寡聚透明质酸-巯基薄荷缩酮载体,制备了载药胶束,制剂形态为球形,粒径在100 nm 左右,Zeta电位为-(21.97±1.08)mV,体外考察证明具有pH及还原敏感性。

     

    Abstract: In order to construct a novel multifunctional targeting nano-carrier based on pH-redox characteristics of tumor microenvironment, ketone bonds and disulfide bonds were bonded to the oligomeric hyaluronic acid(oHA)being sensitive to pH and the reduction environment. The chemical structure of oligomeric hyaluronic acid-8-mercaptomenthone 1, 2-glycerolketal(oHMST)was characterized by 1H NMR, IR and ESI-MS. Curcumin-loaded micelles were prepared by dialysis. The single factor investigation was carried out on the dosage form. Some properties, including particle size zeta potential, the morphology of micelles, and pH-sensitivity were studied. The materials were synthesized successfully. The micelles were spheric with a diameter of about 100 nm. The Zeta potential of the micelles was -(21. 97±1. 08)mV. The in vitro test showed that oHMST carriers have good pH-sensitivity and redox-sensitivity.

     

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