Rational design of an arene ruthenium chlorin conjugate for in vivo anticancer activity

A tetranuclear p-cymene ruthenium 5,10,15,20-tetra(3-pyridyl)chlorin complex has been prepared and evaluated in vivo as dual photosensitizer and chemotherapeutic agent on mice bearing an ectopic human oral carcinoma xenograft. The in vivo study was planned using a statistical model. Optimisations of the treatment factors showed that the injected dose was critical, while the light–drug interval, fluence and fluence rate had only a modest impact. The ruthenium–chlorin conjugate was found to accumulate preferentially in the endoplasmic reticulum of KB cells. In addition, a mode of action in vivo dominated by a cytotoxic effect of the complex and not a photodynamic efficiency of the photosensitizer was suggested.