文章摘要
朱春香,吴轶群,田天立,陈晓庆,张晴,姚勇,葛亮.治疗食管癌的pH敏感多肽水凝胶的设计与研究[J].药学与临床研究,2022,30(6):481~486
治疗食管癌的pH敏感多肽水凝胶的设计与研究
Design and Inspection of pH-Sensitive Peptide Hydrogel for the Treatment of Esophageal Cancer
投稿时间:2022-09-30  修订日期:2022-12-16
DOI:
中文关键词: 食管癌  多肽水凝胶  pH敏感  缓释
英文关键词: Esophageal cancer  Peptide hydrogel  pH-sensitive  Sustained release
基金项目:国家自然科学基金地区科学基金项目(81760638)
作者单位邮编
朱春香 南京高新医院 211800
吴轶群 中国药科大学 
田天立 中国药科大学 
陈晓庆 中国药科大学 
张晴 中国药科大学 
姚勇 中国药科大学 
葛亮 中国药科大学 211100
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中文摘要:
      目的:寻求靶向与缓释能力强且安全高效的阿霉素(DOX)载体以提高食管癌治疗效果。方法:设计序列为FOVVVEF(苯丙氨酸-鸟氨酸-缬氨酸-缬氨酸-缬氨酸-谷氨酸-苯丙氨酸)的多肽;调整多肽浓度、DOX浓度以及pH验证该多肽的成胶能力;通过透射电子显微镜(TEM)、圆二色谱、流变学检测、药物释放以及体外细胞实验考察水凝胶的微观形态、二级结构、机械强度、pH敏感性、生物相容性以及体外抗肿瘤活性。结果:通过固相多肽合成法合成的多肽纯度 > 95%,其质谱测得的分子量与理论值相符。该多肽能够在多肽浓度为20 mg·mL-1、DOX浓度为2 mg·mL-1、pH为7.4时形成稳定的载药水凝胶,其构象以β-折叠为主同时具有良好的机械性能,在pH 5.8时由于质子化程度增强,二级结构瓦解,药物释放增加。结论:该pH敏感性的多肽水凝胶同时具备良好的生物相容性与优异的体外抗肿瘤活性。
英文摘要:
      Objective: A safe and efficient drug carrier with strong sustained release ability is designed and tested to improve the therapeutic effect of doxorubicin (DOX) in treating esophageal cancer. Methods: In this project, a peptide with the sequence FOVVVEF was designed. The gel-forming ability of this peptide was verified by adjusting pH and the concentrations of the peptide and the anti-tumor drug DOX. The micromorphology, secondary structure, mechanical strength, pH sensitivity, biocompatibility and in vitro anti-tumor activity of the hydrogel were investigated by TEM, circular dichroism, rheological detection, drug release and in vitro cell experiments. Results: The purity of the peptide synthesized by a solid-phase method was higher than 95% and the molecular weight measured by mass spectrometry was consistent with the theoretical value. The peptide formed a stable drug-loaded hydrogel under pH 7.4 when the concentrations of peptide and DOX were 20 mg·mL-1 and 2 mg·mL-1, respectively. The conformation of the hydrogel was dominated by β-sheet and it had good mechanical properties. The secondary structure collapsed and the amount of drug release increased due to the enhanced protonation. Meanwhile, the peptide hydrogel had both good biocompatibility and excellent in vitro antitumor activity. Conclusion: A pH-sensitive peptide hydrogel has been successfully prepared which is strongly potent in the treatment of esophageal cancer.
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