Department of General Surgery, Zhoupu Hospital of Shanghai Pudong New Area, Shanghai, China.
Cancer Biol Ther. 2012 Dec;13(14):1407-16. doi: 10.4161/cbt.22001. Epub 2012 Sep 6.
Biodegradable polymer nanoparticle drug delivery systems are characterized by targeted drug delivery, improved pharmacokinetic and biodistribution, enhanced drug stability and lowered side effects; these drug delivery systems are widely used for delivery of cytotoxic agents. The galactosylated chitosan (GC)/5-fluorouracil (5-FU) nanoparticle is a nanomaterial made by coupling GC, a polymer known to have the advantages described above, and 5-FU. The GC/5-FU nanoparticle is a sustained release system, it was showed that the peak time, half-life time, mean residence time (MRT) and area of under curve (AUC) of GC/5-FU were longer or more than those of the 5-FU group, but the maximum concentration (Cmax) was lower. The distribution of GC/5-FU in vivo revealed the greatest accumulation in the hepatic cancer tissues, and the hepatic cell was the target of the nanoparticles. Toxicology research showed that the toxicity of GC-5-FU was lower than that of 5-FU in mice. In vivo experiments showed that GC/5-FU can significantly inhibit tumor growth in an orthotropic liver cancer mouse model. GC/5-FU treatment can significantly lower the tumor weight and increase the survival time of mice when compared with 5-FU treatment alone. Flow cytometry and the TUNEL assay revealed that compared with 5-FU, GC/5-FU caused higher rates of G 0-G 1 arrest and apoptosis in hepatic cancer cells.
可生物降解聚合物纳米药物传递系统的特点是靶向药物传递、改善药代动力学和生物分布、增强药物稳定性和降低副作用；这些药物传递系统广泛用于细胞毒性药物的传递。半乳糖化壳聚糖（GC）/5-氟尿嘧啶（5-FU）纳米粒是一种纳米材料，通过将 GC 与 5-FU 偶联而成，GC 是一种具有上述优点的聚合物。GC/5-FU 纳米粒是一种缓释系统，结果表明，GC/5-FU 的达峰时间、半衰期、平均驻留时间（MRT）和曲线下面积（AUC）均长于或大于 5-FU 组，但最大浓度（Cmax）较低。GC/5-FU 的体内分布显示在肝癌组织中有最大的蓄积，肝细胞核是纳米粒的靶标。毒理学研究表明，GC-5-FU 的毒性低于 5-FU 在小鼠中的毒性。体内实验表明，GC/5-FU 能显著抑制原位肝癌小鼠模型的肿瘤生长。与 5-FU 单独治疗相比，GC/5-FU 治疗可显著降低肿瘤重量并延长小鼠的生存时间。流式细胞术和 TUNEL 检测显示，与 5-FU 相比，GC/5-FU 可导致肝癌细胞中 G0-G1 期阻滞和凋亡的比例更高。
