Resistance is a common issue with many medicines; cancer chemotherapeutics are no exception, moreover cross resistance can be induced by one agent against a number of chemically or functionally related compounds.
This resistance is characteristically mediated by over-expression of certain cellular efflux pumps. The passage of drugs through the nuclear envelope is a particular area of interest to us, as many anti-cancer agents’ action is against chromososomal material. In order to study the movements of drugs in resistant and sensitive cells, we have used autofluorescent anthracyclines, including administration by micro-injection and labelled membrane markers. An approach to these problems avoiding the use of labels that might compromise a drug’s properties, we are investigating the use of mid-range and near infra-red spectroscopy – combined with imaging to visualise the movement of native, non-fluorescent drugs and to pick up changes in cellular metabolism: so called optical biopsy methods.