Nuclear drug delivery to target tumour cells

Cancer remains one of the leading causes of death worldwide. Although enticing, the concept of a chemotherapeutic treatment directed towards a single target that kills turnout cells, without any harmful side effects or death of neighbouring cells is probably naive, due to the fact that turnout cells arise from normal cells and share many common biological features with them. Various means to damage/destroy turnout cells preferentially have been developed, but as yet, none are truly selective. However, by combining numerous tumour-specific/-enhanced targeting signals into a single modular multifaceted approach, it may prove possible some time in the future to achieve the desired outcome, without any unwanted bystander effects, with the delivery of cytotoxic drugs/DNA directly to the nucleus specifically within tumour cells of great interest in this context. To achieve this, modules such as the tumour-specific nuclear targeting signal of the chicken anemia virus Apoptin protein represent exciting possibilities. The present review discusses the question of nuclear delivery of bioactive molecules and its associated problems, as well as recent progress towards the development of tumour-specific modular recombinant transporters as viable anti-cancer therapeutics. In particular we focus upon the incorporation of turnout cell-selective nuclear targeting into these systems as a means to deliver cytotoxic genes or drugs to the very heart of turnout cells. (C) 2009 Elsevier B.V. All rights reserved.