Esterase-induced release of a theranostic prodrug in lysosomes for improved therapeutic efficacy and lower systemic toxicity.

ABSTRACT: 5-Fluorouracil (5-FU) is the third most used chemotherapeutic agent. Despite being a frontline drug, it inhibits thymidylate synthase in malignant and non-malignant cells, which adds to its severe systemic toxicity. To address this, a new physiologically benign theranostic prodrug of 5-FU, named PD, has been developed by covalently linking 5-FU with a fluorophore and a lysosome-targeting morpholine moiety through an ester functionality. Esterase (Est), being overexpressed in various cancer cells such as human glioblastoma (U87) cells and human ovarian cancer (SKOV-3) cells, induces cleavage of the ester linkage and results in a sustained release of 5-fluorouracil-1-acetic acid (FUA), a precursor that liberates 5-FU in human physiology and subsequently 5-FU in lysosomes. The higher efficacy

SUBMITTER: Dutta S 

PROVIDER: S-EPMC12362862 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature