As the approach frequently applied to overcome such a therapeutic limitation, targeted delivery provides a route for facilitating the MTX uptake by a cancer cell, and as a consequence, for enhancing its therapeutic index 4, 6- 7, 22. Despite its proven therapeutic value in the treatment of certain cancers 20 and rheumatoid arthritis 21, MTX suffers from its non-selective cytotoxicity that contributes to lower its therapeutic index 17. It is a potent inhibitor ( K i = 0.058 nM 16) of dihydrofolate reductase (DHFR 18- 19) localized in the cytoplasm. MTX belongs to a class of antifolate molecules and constitutes one of the clinically approved anticancer drugs 1, 16- 17. The drug release can be controlled by the mechanism triggered by an endogenous factor (low pH, reduction, enzymes), or an external tool such as light. The rate of the drug release varies in response to multiple control parameters, including linker design, light wavelength, exposure time, and the pH of the medium where the drug release occurs.Ī proposed schematic illustrating the concept of cancer targeting drug delivery. This article reports that methotrexate is released by the photochemical mechanism in an actively controlled manner. We performed the drug release studies by using a combination of three standard analytical methods that include UV/vis spectrometry, 1H NMR spectroscopy, and anal. We evaluated two types of the o-nitrobenzyl-linked methotrexate for the drug release study and further extended the study to a fifth-generation poly(amidoamine) dendrimer carrier covalently conjugated with methotrexate via the o-nitrobenzyl linker. This study investigates the light-mediated release of methotrexate, an anticancer drug, using a photocleavable linker strategy based on o-nitrobenzyl protection. ![]() Photochemistry provides a unique mechanism that enables the active control of drug release in cancer-targeting drug delivery.
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