乳腺癌靶向还原敏感聚酯酰胺纳米药物的研制
Breast Cancer Targeted Reduction-Sensitive Poly(ester amide) Nanomedicines
本文设计合成了侧链接枝透明质酸（HA）的还原敏感的聚酯酰胺（SSPEAs）得到SSPEA-HA，并初步研究了由其制备的纳米粒作为靶向乳癌细胞的药物载体的可能性。SSPEA-HA通过溶液缩聚和迈克尔加成便捷制备，其中二硫键和透明质酸的含量可通过改变单体的比例来调节。SSPEA-HA在水溶液中可自组装形成粒径100 nm以下、分布窄的纳米粒。该纳米粒具有还原敏感性，其在生理环境下储存粒径几乎没有变化，而在模拟肿瘤细胞内还原环境下不稳定，很快发生溶胀。此外，该纳米粒可高效装载疏水抗癌药物阿霉素（DOX），体外药物释放实验结果表明，载DOX纳米粒在模拟细胞内还原环境下可快速释放DOX（累计释放量 > 80%），而对照组释放缓慢（累计释放量 ~ 20%）。细胞毒性实验表明，SSPEA-HA纳米粒具有良好的生物相容性。因此，该SSPEA-HA纳米制备的纳米药物有望在CD44过表达的乳腺癌的主动靶向治疗中有较好疗效。
In this paper, a reduction-sensitive Poly(ester amide)s (SSPEA) grafted with hyaluronic acid (HA) were designed and synthesized (SSPEA-HA) and their nanoparticles were investigated for breast cancer-targeting delivery of DOX. By using polycondensation reaction and Michael addition reaction, SSPEA-HA were readily obtained. The contents of disulfides and HA were readily tuned by manipulating the monomer ratios. The self-assembled nanoparticles have small size (< 100 nm) and narrow size distributions. SSPEA-HA nanoparticles tended to be unstable in reduction enviroment, exhibiting reduction-sensitivity. They exibited a decent DOX loading capacity, and DOX-loaded nanoparticles showed apparent reduction sensitivity with > 80% DOX release within 12 h in the presence of 10 mM GSH, as compared to their little release (~ 20%) in the absence of GSH and the reduction insensitive control PEA-HA nanoparticles. MTT assays showed that SSPEA-HA nanoparticles were non-toxic. Therefore, SSPEA-HA nanoparticles have potential in targeted therapy of CD44 overexpressing breast cancers.
吕娇龙、孟凤华、钟伊南
肿瘤学药学生物工程学
高分子化学聚酯酰胺透明质酸纳米粒还原敏感乳癌靶向
polymer chemistrypoly(ester amide)hyaluronic acidnanoparticlesreduction sensitivitybreast cancer-targeting
吕娇龙,孟凤华,钟伊南.乳腺癌靶向还原敏感聚酯酰胺纳米药物的研制[EB/OL].(2017-04-28)[2025-08-24].http://www.paper.edu.cn/releasepaper/content/201704-822.点此复制
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