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• W2912176006 abstract "Gemcitabine (Gem) as an anti-cancer agent has been limited by its short circulation time and rapid metabolism that reflects in low tumor uptake and low therapeutic efficiency. To improve its anti-tumor activity, a novel FAPα enzyme-activated prodrug of Z-GP-Gem modified at 4-amino group of Gem was developed, which could effectively release parent Gem based on the specific cleavage via FAPα enzyme-activation in tumor microenvironment. Compared to Gem, the Z-GP-Gem prodrug exhibited significantly enhanced inhibition of both tumor growth and pulmonary metastasis in BALB/c mice bearing orthotopic breast 4T1 tumors. The Z-GP-Gem prodrug has a prolonged circulation time and a high tumor uptake based on the modification of Z-GP dipeptide at 4-amino group of Gem. These eventually caused a marked improvement in the systemic toxicity and the tumor growth inhibition in 4T1 cells. More interestingly, the unexpected depletion of tumor-associated fibroblast (TAF) was observed during the treatment of Z-GP-Gem prodrug in animal model. Therefore, these findings demonstrated that the FAPα-activated prodrug Z-GP-Gem would be a desirable approach for tumor therapy by intravenous administration." @default.
• W2912176006 created "2019-02-21" @default.
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• W2912176006 date "2019-03-01" @default.
• W2912176006 modified "2023-10-16" @default.
• W2912176006 title "Enhanced anti-tumor efficiency of gemcitabine prodrug by FAPα-mediated activation" @default.
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• W2912176006 doi "https://doi.org/10.1016/j.ijpharm.2019.01.032" @default.
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