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使用药物和基因共递送的靶向聚乙二醇-ε-聚己内酯纳米载体的结直肠癌联合治疗

Colorectal cancer combination therapy using drug and gene co-delivered, targeted poly(ethylene glycol)-ε-poly(caprolactone) nanocarriers.

作者信息

Wang Zhiyu, Wei Yaning, Fang Guotao, Hong Dan, An Lin, Jiao Ting, Shi Yan, Zang Aimin

机构信息

Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding 071000, People's Republic of China,

出版信息

Drug Des Devel Ther. 2018 Sep 24;12:3171-3180. doi: 10.2147/DDDT.S175614. eCollection 2018.

Abstract

PURPOSE

Combination therapy is a promising strategy to treat cancer due to the synergistic effects. The drug and gene co-delivered systems attract more attention in the field of combination therapy.

MATERIALS AND METHODS

In the present research, poly(ethylene glycol)-ε-poly(caprolactone) block copolymer was used for the co-loading of 5-fluorouracil (5-FU) and gene. The physicochemical characteristics, in vitro and in vivo anticancer, and gene transfection efficiency were tested on colon cancer cells and tumor-bearing mice.

RESULTS

5-FU and gene co-loaded nanocarriers had a size of 145 nm. In vivo gene delivery results showed about 60% of gene-positive cells. Tumor volume of nanocarrier groups at day 21 was around 320 mm, which is significantly smaller compared with free 5-FU group (852 mm) and control group (1,059 mm). The maximum 5-FU plasma concentration in nanocarrier groups (49 µg/mL) was significantly greater than free 5-FU (13 µg/mL). At 24 hours, drug level of nanocarrier groups was about 2.8 µg/mL compared with 0.02 µg/mL of free 5-FU.

CONCLUSION

The resulting nanocarriers co-loaded with the anticancer drugs and genes could be considered as a promising nanomedicine for colorectal cancer therapy.

摘要

目的

联合治疗因具有协同效应而成为一种很有前景的癌症治疗策略。药物与基因共递送系统在联合治疗领域备受关注。

材料与方法

在本研究中,聚乙二醇-ε-聚己内酯嵌段共聚物用于共同负载5-氟尿嘧啶(5-FU)和基因。对结肠癌细胞和荷瘤小鼠测试了其理化特性、体外和体内抗癌效果以及基因转染效率。

结果

负载5-FU和基因的纳米载体粒径为145 nm。体内基因递送结果显示约60%的基因阳性细胞。纳米载体组在第21天的肿瘤体积约为320 mm,与游离5-FU组(852 mm)和对照组(1059 mm)相比显著更小。纳米载体组的最大5-FU血浆浓度(49 μg/mL)显著高于游离5-FU(13 μg/mL)。在24小时时,纳米载体组的药物水平约为2.8 μg/mL,而游离5-FU为0.02 μg/mL。

结论

所得到的负载抗癌药物和基因的纳米载体可被视为一种很有前景的用于结直肠癌治疗的纳米药物。

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