Tang Qingchao, Wang Yihui, Huang Rui, You Qi, Wang Guiyu, Chen Yinggang, Jiang Zheng, Liu Zheng, Yu Lei, Muhammad Shan, Wang Xishan
Department of Colorectal Cancer Surgery, Cancer Center, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.
Department of Colorectal Surgery, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
PLoS One. 2014 Jun 4;9(6):e98455. doi: 10.1371/journal.pone.0098455. eCollection 2014.
5-Fluorouracil (5-FU) is one of the most classic chemotherapy drugs. Nanoparticle drug delivery vehicles offer superiority over target effect enhancement and abatement of side effects. Little is known however as to the specific effect of nanoparticle on peritoneal dissemination of colon cancer. The aim of this study is to prepare one NPs (nanoparticles) loaded with 5-FU and investigate the characteristic of NPs and the role of it in peritoneal metastasis nodules formation of human colon cancer.
METHODOLOGY/PRINCIPAL FINDINGS: Prepared the NPs (nanoparticles) loaded with 5-FU (5-Fluorouracil) by PEG-PLGA with the method of double emulsion. Then evaluate the characteristics of the NPs by scanning electron microscopy, analyzing the particle diameter distribution and determining the loading efficiency. Detect the release features of NPs in vitro and in vivo. Nude mice with peritoneal metastases were treated with 5-FU solution or 5-FU-NPs through peritoneal cavity. Count the nodules on peritoneum and mesenterium and survey the size of them. We got NPs with average-diameter of 310 nm. In vitro release test shows NPs can release equably for 5 days with release rate of 99.2%. In vivo, NPs group can keep higher plasma concentration of 5-FU longer than it in solution group. The number of peritoneal dissemination nodule below 1 mm in 5-FU-sol group(17.3 ± 3.5) and 5-FU-NP group(15.2 ± 3.2) is less than control group(27.2 ± 4.7)(P<0.05). The total number of nodules in 5-FU-NP group(28.7 ± 4.2) is significantly smaller than in 5-FU-sol group(37.7 ± 6.3) (P<0.05).
CONCLUSIONS/SIGNIFICANCE: The novel anti-tumor nanoparticles loaded with 5-FU by PEG-PLGA can release maintain 5 days and have inhibitory action to peritoneal dissemination of colon cancer in mice.
5-氟尿嘧啶（5-FU）是最经典的化疗药物之一。纳米颗粒药物递送载体在增强靶向效应和减轻副作用方面具有优势。然而，关于纳米颗粒对结肠癌腹膜播散的具体作用知之甚少。本研究的目的是制备一种负载5-FU的纳米颗粒（NPs），并研究其特性以及在人结肠癌腹膜转移结节形成中的作用。
方法/主要发现：采用双乳化法用聚乙二醇-聚乳酸-羟基乙酸共聚物（PEG-PLGA）制备负载5-氟尿嘧啶（5-FU）的纳米颗粒（NPs）。然后通过扫描电子显微镜评估纳米颗粒的特性，分析粒径分布并测定载药效率。检测纳米颗粒在体外和体内的释放特性。对患有腹膜转移的裸鼠通过腹腔注射5-FU溶液或5-FU-NPs进行治疗。计数腹膜和肠系膜上的结节并测量其大小。我们得到了平均直径为310 nm的纳米颗粒。体外释放试验表明纳米颗粒可均匀释放5天，释放率为99.2%。在体内，纳米颗粒组比溶液组能更长时间维持较高的5-FU血浆浓度。5-FU溶液组（17.3±3.5）和5-FU-NP组（15.2±3.2）中直径小于1 mm的腹膜播散结节数量少于对照组（27.2±4.7）（P<0.05）。5-FU-NP组的结节总数（28.7±4.2）明显少于5-FU溶液组（37.7±6.3）（P<0.05）。
结论/意义：通过PEG-PLGA负载5-FU的新型抗肿瘤纳米颗粒可维持5天释放，并对小鼠结肠癌腹膜播散具有抑制作用。
