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

다국어 초록 (Multilingual Abstract)

Widely used chemotherapeutic agent 5‐fluorouracil (5‐Fu) exhibits adverse effects by damaging the normal cells. Controlled 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.
A design of low molecular weight hydrogelator peptide‐drug conjugate is demonstrated for the photo‐controlled delivery of chemotherapeutic agent 5‐Fluorouracil (5‐Fu). The molecule was synthesized by covalent attachment of 5‐Fu with phenylalanine dipeptide through a photo‐cleavable linker. The peptide 5‐Fu conjugate was able to form organogel as well as hydrogel. The hydrogel was formed within a narrow pH window (pH 6.0 ‐ 8.0). The molecule was proved to be non‐toxic in HeLa cells. The designed hydrogelator could be useful for controlled delivery of 5‐Fu.