Synthesis of a Peptide Conjugated 5-Fluorouracil Gelator Prodrug for Photo-Controlled Release of the Antitumor Agent

摘要

Widely used chemotherapeutic agent 5-fluorouracil (5-Fu) exhibits adverse effects by damaging the normal cells. Con- trolled delivery and release of such antitumor drugs is essential for better treatment. Herein, a low molecular weight peptide- drug conjugate for the photo-controlled delivery of 5-Fu is demonstrated. 5-Fu is covalently attached with a short peptide through a photo-cleavable linker. With a careful choice of the peptide sequence, the peptide-drug conjugate was able to form a hydrogel within a narrow pH window (pH 6.0 - 8.0). MTT assay of the peptide-drug conjugate in HeLa cells inferred almost no cytotoxicity up to a high concentration of 110 μg/ mL. The gelator prodrug releases 5-Fu in a controlled, does- dependent manner under irradiation. The characterizations and controlled release of the drug were investigated using various analytical techniques including FTIR, HPLC and UV-visible spectroscopy whereas, morphology of the gel was studied by FESEM. The gelation behaviour and rheology of the conjugate was also studied in details. Such covalently peptide-conjugated 5-Fu gel could be useful for effective delivery of antitumor agent.