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

摘要

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.