Structure–activity relationship of polyamine conjugates for uptake via polyamine transport system

Abstract

High toxicity of anticancer drugs led to development of targeted drug delivery directly to the specific organs. Polyamine transport system (PTS) of mammalian cells is one of the targets for a cell-selective drug delivery of polyamine–drug conjugates into specific organs. Even without having a 3D structure for mammalian PTS, synthesis of polyamine derivatives and evaluation of their cytotoxic effects are potential practical approaches to find optimal polyamine moieties to be transported from the PTSs. Chinese hamster ovary (CHO) and its mutant cell line (CHO-MG) are two important cells for evaluation of polyamine transportation by polyamine transporters (PAT). If a polyamine conjugate ligand demonstrates a high IC50 ratio on CHO-MG/CHO cells, this indicates a high selectivity of such compound toward PAT. This study discussed the structural requirements (charge, linker, vector, cargo) of polyamine conjugates in order to be transported into the cells by the mean of PTS.