Development of tumour targeted nanoparticles
Anthracycline and anthracenedione anticancer agent primarily induce topoisomerase II poisoning which leads to accumulation of lethal double-strand DNA breaks in cancer cells. The objective is to improve the effectiveness of these widely used anticancer drugs using targeted nanoparticle therapy. Our research addresses the serious side-effects of the anthracycline drugs, also potentially enabling lower doses to be employed. One aspect of this study encapsulates anthracyclines and anthracenediones in the nanoparticles for tumour-specific drug delivery.
We also endeavour to increase the anticancer potency of anthracyclines by developing nanoparticles for localised formaldehyde release in the tumour environment. This requires the development of a carrier system to protect formaldehyde-releasing prodrugs from non-specific esterase-mediated hydrolysis, allowing them to biodistribute intact to tumour tissue. A dramatic tumour growth inhibitory response to our combination treatment in a 'triple negative' MDA-MB-231 breast tumour model indicates that such a treatment strategy could be particularly useful for such tumours in the clinic.
This study requires us to take a multidisciplinary approach in our research which incorporates expertise in a range of diverse areas including drug-DNA interactions, cell biology, nanotechnology, biomolecular surface analysis, medicinal chemistry and preclinical drug evaluation.