Receptor mediated endocytosis for drug delivery in African trypanosomes: fulfilling Paul Ehrlich’s vision of chemotherapy
(featured on the front cover of the May 2013 edition of Trends in Parasitology)
A lot of time is spent identifying candidate drug targets and then designing inhibitors to block their function in the ‘test tube’. Unfortunately, though highly effective on the bench, many of these compounds fail when used against their target pathogen. Therefore, it’s of fundamental importance to consider how any inhibitor is to enter the target cell, whether by passive diffusion through the membrane, uptake via a membrane channel, or by receptor mediated endocytosis.
We argue that receptor-mediated endocytosis (RME) represents a robust validated route for the entry of drugs into African trypanosomes (and probably any other pathogen). Recent developments in our understanding of the uptake of suramin (Alsford et al, 2012) and human serum trypanolytic factors (Higgins et al, 2013) have shown just how effective RME is at taking up trypanocidal agents. Using these compounds, and others, as chemical probes will enable us to expand our understanding of the network of proteins underlying and driving RME. Further, this may lead to the identification of specific essential pathways that can be exploited for drug uptake and which are less vulnerable to the development of drug resistance.