Anticancer activity of polymeric nanoparticles containing linoleic acid-SN38 (LA-SN38) conjugate in a murine model of colorectal cancer
Anticancer activity of polymeric nanoparticles containing linoleic acid-SN38 (LA-SN38) conjugate in a murine model of colorectal cancer
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含有亚油酸-SN38（LA-SN38）缀合物的聚合物纳米粒子在结直肠癌小鼠模型中的抗癌活性
DOI：
10.1016/j.colsurfb.2019.06.020
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发表时间：
2019-09-01
影响因子：
5.8
通讯作者：
Yu, Bo
中科院分区：
文献类型：
--
作者：
Cheng, Guilin;Zhang, Xiaomin;Yu, Bo
可生物降解的聚合物纳米颗粒（NP）经常用作抗癌药物的纳米载体。采用可生物降解的聚环氧乙烷-聚环氧丁烷（PEO-PBO）二嵌段共聚物，通过滴定水合法，不使用有毒有机溶剂，开发了亚油酸共轭SN38（LA-SN38）负载的纳米颗粒（EBNP）。 EBNPs 对 LA-SN38 具有较高的载药效率和包封率，分别为 7.53% 和 93.55%。多分散指数(PDI)和平均直径分别为0.173+/-0.019和226.1+/-1.2nm。透射电子显微镜（TEM）图像显示纳米颗粒尺寸均匀且具有球形结构。体外研究表明 EBNP 的释放行为缓慢且持续。此外，细胞毒性和细胞凋亡实验证明EBNPs对人结肠癌细胞的生长抑制更有效。细胞摄取实验进一步证明EBNPs可以避免巨噬细胞的吞噬作用并促进癌细胞的摄取。在体内，EBNPs具有延长的血液循环时间和生物分布的肿瘤选择性。 EBNPs的抑瘤率高于SNPs组和CPT-11组（P < 0.01），且在测试剂量下药物未表现出明显的全身毒性。这些结果表明 EBNP 是用于递送 LA-SN38 治疗结直肠癌的有希望的候选者。
Biodegradable polymeric nanoparticles (NPs) have been used frequently as nanocarriers for anticancer drugs. Linoleic acid conjugated SN38 (LA-SN38)-loaded NPs (EBNPs) were developed using biodegradable poly (ethylene oxide)-poly (butylene oxide) (PEO-PBO) diblock copolymer by titration hydration method without using a toxic organic solvent. The EBNPs had high drug loading efficiency and entrapment efficiency for LA-SN38, at 7.53% and 93.55%, respectively. The polydispersity index (PDI) and average diameter were 0.173 +/- 0.019 and 226.1 +/- 1.2 nm, respectively. The transmission electron microscope (TEM) image presented that the NPs were homogeneous in size and had spherical structures. In vitro study showed the release behavior of EBNPs was slow and sustained. Furthermore, cytotoxicity and apoptosis assay proved that EBNPs were more effective in growth inhibition of human colon cancer cells. Cell uptake experiments further demonstrated that EBNPs could avoid the phagocytosis by macrophages and promote the uptake by cancer cells. In vivo, EBNPs had prolonged blood circulation time and tumor selectivity in biodistribution. The tumor inhibitory rate of EBNPs was higher compared to SNPs group and CPT-11group (P < 0.01), and the drug did not show significant systemic toxicity at the tested dose. These results indicated that EBNPs are a promising candidate for delivery of LA-SN38 to treat colorectal cancer.