王定福,仇晓雷,郝丽桦,等.聚古罗糖醛酸硫酸酯-铜纳米胶束制备及抗肿瘤活性研究[J].中国海洋药物,2022,41(2):55-61. |
聚古罗糖醛酸硫酸酯-铜纳米胶束制备及抗肿瘤活性研究 |
Preparation and antitumor activity of polyguluronate sulfate-copper nanomicelles |
投稿时间:2021-05-06 修订日期:2021-05-17 |
DOI: |
中文关键词: 聚古罗糖醛酸硫酸酯 聚电解质纳米胶束 化学动力学疗法 抗肿瘤 |
English Keywords:Polyguluronate sulfate Polyelectrolyte nanomicelles Chemodynamic therapy Antitumor |
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中文摘要: |
目的 制备一种基于化学动力学疗法的聚古罗糖醛酸硫酸酯(PGS)-铜纳米胶束,进行抗肿瘤活性研究。方法 采用聚离子复合法,将PGS与铜离子及过氧化氢反应制备聚电解质纳米胶束PGS-Cu,分光光度法测定铜离子含量和羟基自由基,CCK-8法测定细胞活力。结果 制备的PGS-Cu纳米粒径为109.54±14.29 nm,分布系数为0.23±0.02,Zeta电位为-47.58±1.71 mV。酸性环境下,PGS-Cu纳米胶束铜离子累积释放量显著高于中性环境,并产生.OH。100 μg.mL-1的PGS-Cu纳米胶束作用下,人源三阴性乳腺癌细胞(MDA-MB-231)、小鼠乳腺癌细胞(4T1)和小鼠正常成纤维细胞(NIH/3T3)的活力分别为14.87%,62.24%和90.77%,表明PGS-Cu纳米胶束对乳腺癌细胞有显著的细胞毒性,且对MDA-MB-231细胞抑制效果最佳。此外,4T1细胞在pH 7.4和6.0时的活力分别为62.24%和18.33%,说明该纳米胶束具有pH响应性。结论成功构建了一种基于化学动力学疗法、以多糖为载体的聚电解纳米胶束,该纳米胶束具有pH响应性和肿瘤靶向性,能有效抑制乳腺癌细胞生长,发挥抗肿瘤活性。 |
English Summary: |
Objective To Prepare polyguluronate sulfate (PGS)-copper nanomicelle to achieve chemodynamic therapy for tumor treatment. Methods PGS-Cu nanomicelles were prepared by polyion combination method; copper ion content and hydroxyl radicals were determined by spectrophotometry; and breast cancer cell viability was measured by CCK-8 method. Results The PGS-Cu nanomicelles were prepared with particle size of 109.54±14.29 nm, distribution coefficient of 0.23±0.02, and zeta potential of -47.58±1.71 mV. The cumulative release of copper ions from PGS-Cu nanomicelles was significantly higher in acidic environment than in neutral environment, and .OH was generated. At the dose of 100 μg.mL-1, the viabilities of human-derived triple-negative breast cancer cells (MDA-MB-231), mouse breast cancer cells (4T1) and mouse normal fibroblasts (NIH/3T3) were 14.87%, 62.24% and 90.77%, respectively. The results indicated that PGS-Cu nanomicelles were significantly cytotoxic to breast cancer cells and had the best inhibitory effect on MDA-MB-231 cells. In addition, the viabilities of 4T1 cells at pH 7.4 and 6.0 were 62.24% and 18.33%, respectively, indicating that the nanomicelles were of pH-response. Conclusion A kind of chemodynamic-therapy-based polyelectrolytic nanomicelle with polysaccharide as a nanocarrier was successfully constructed with pH-response and tumor-targeting and can effectively inhibit the growth of breast cancer cells and exert anti-tumor activity. |
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