Radiation- and Photo-induced Activation of 5-Fluorouracil Prodrugs as a Strategy for the Selective Treatment of Solid Tumors

Abstract

5-Fluorouracil (5-FU) is used widely as an anticancer drug to treat solid cancers, such as colon, breast, rectal, and pancreatic cancers, although its clinical application is limited because 5-FU has gastrointestinal and hematological toxicity. Many groups are searching for prodrugs with functions that are tumor selective in their delivery and can be activated to improve the clinical utility of 5-FU as an important cancer chemotherapeutic agent. UV and ionizing radiation can cause chemical reactions in a localized area of the body, and these have been applied in the development of site-specific drug activation and sensitization. In this review, we describe recent progress in the development of novel 5-FU prodrugs that are activated site specifically by UV light and ionizing radiation in the tumor microenvironment. We also discuss the chemical mechanisms underlying this activation.

A Polymeric Drug Depot Based on 7‐(2′‐Methacryloyloxyethoxy)‐4‐methylcoumarin Copolymers for Photoinduced Release of 5‐Fluorouracil Designed for the Treatment of Secondary Cataracts

“…The organic phase was dried with magnesium sulfate before the solvent was removed under reduced pressure. Recrystallization from an ethanol/ methanol mixture (1:1) gave 7-(2 0 -Methacryloyloxyethoxy)-4-methylcoumarin (3) 13 …”

“…Recently, we and others reported a novel photoresponsive drug‐delivery system for intraocular lenses used in cataract surgery, equipped with a multidose pro‐drug (1‐heptanoyl‐5‐fluorouracil) depot as an alternative way to treat PCO 8–12. 5‐Fluorouracil (5FU) is a well‐studied chemotherapeutic agent and, recently, an interesting review article on the radiation and photoinduced activation of 5FU pro‐drugs for selective treatment of cancers was published 13. A pro‐drug is a chemically modified form that is converted to the active form of the drug in the biological system and exerts its effect 14.…”

“…[8][9][10][11][12] 5-Fluorouracil (5FU) is a well-studied chemotherapeutic agent and, recently, an interesting review article on the radiation and photoinduced activation of 5FU pro-drugs for selective treatment of cancers was published. [13] A pro-drug is a chemically modified form that is converted to the active form of the drug in the biological system and exerts its effect. [14] Acylation of the actual cytostatic drug, 5-fluorouracil, with heptanoic acid chloride is necessary in this work because of the very low solubility of 5-fluorouracil in organic solvents.…”

A novel o-nitrobenzyl-based photocleavable antitumor prodrug with the capability of releasing 5-fluorourail

“…All over the world, considerable efforts have been invested in prevention, diagnosis, and treatment of cancer [1,2]. Currently, 5-fluorouracil (5-Fu) is the most widely used anticancer drug and thymidylate synthase inhibitor that can inhibit the proliferation of tumor cells by affecting metabolism of DNA and RNA [3].…”

Synthesis and one-electron reduction characteristics of radiation-activated prodrugs possessing two 5-fluorodeoxyuridine units

“…The use of stimuli-responsive prodrugs offers an interesting opportunity for the efficient and precise onset of drug potency. 10,11 One new strategy is the use of X-irradiation as an external trigger to activate a prodrug. [12][13][14][15][16][17] Since the chemical reactions triggered by this stimulation can be controlled spatially and temporally, the prodrug can be converted to its active form with exact control over the area, time, and dosage.…”