Delivery and release of curcumin by a hypoxia-activated cobalt chaperone: a XANES and FLIM study

Abstract

We present a bioreductively activated cobalt(III) carrier system for the delivery of curcumin with enhanced drug stability, tumour penetration and efficacy in hypoxic tumour regions. Curcumin is a natural product with potent anticancer activity but low bioavailability and serum stability. With the aim of overcoming these limitations, we prepared a cobalt(III) prodrug of curcumin and compared the stability, cytotoxicity and cellular uptake with those of the free drug. Using a combination of fluorescence lifetime imaging and X-ray absorption spectroscopy, we demonstrated that curcumin is released from the cobalt carrier complex in tumour cells, with strong evidence to suggest that the process occurs via reduction of the cobalt centre. Furthermore, fluorescence lifetime imaging in solid tumour models showed that the cobalt complex delivered curcumin uniformly throughout the tumour model, while free curcumin only accumulated on the outer edges. For comparison, we also investigated the isoelectronic ruthenium(II) complex and found its properties and biological activity to be very different to those of the cobalt analogue.