Drug design, development and therapy · 2018
Colorectal cancer combination therapy using drug and gene co-delivered, targeted poly(ethylene glycol)-ε-poly(caprolactone) nanocarriers.
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Wang Zhiyu, Wei Yaning, Fang Guotao, Hong Dan, An Lin, Jiao Ting, Shi Yan, Zang Aimin
Аннотация
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 mm3, which is significantly smaller compared with free 5-FU group (852 mm3) and control group (1,059 mm3). 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.
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 mm3, which is significantly smaller compared with free 5-FU group (852 mm3) and control group (1,059 mm3). 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.