Synthesis, characterisation and systematic comparison of FITC-labelled GnRH-I, -II and -III analogues on various tumour cells

Targeted tumour therapy is in the focus of recent cancer research. GnRH analogues are able to deliver anticancer agents selectively into tumour cells which highly express GnRH receptors. However, the effectiveness of different analogues as targeting moiety in drug delivery systems is rarely compared and the investigated types of cancers are also limited. Therefore, we prepared selectively labelled, fluorescent derivatives of GnRH-I, -II, and -III analogues which successfully used for drug targeting. In this manuscript we investigated these analogues solubility, stability, passive membrane permeability and compared their cellular uptake by various cancer cells. We found that these labelled GnRH conjugates provide great detectability, without undesired cytotoxicity and passive membrane permeability. The introduced experiments with these conjugates proved their reliable tracking, quantification and comparison. Cellular uptake efficiency was studied on human breast, colon, pancreas and prostate cancer cells (MCF-7, HT-29, BxPC-3, LNCaP) and on dog kidney cells (MDCK). Each of the three conjugates were taken up by GnRH-I receptor expressing cells, but the different cells preferred different analogues. Furthermore, we demonstrated for the first time the high cell surface expression of GnRH-I receptors and the effective cellular uptake of GnRH analogues on human pharynx tumour (Detroit-562) cells. In summary, our presented results detail that the introduced conjugates could be innovative tools for the examination of the GnRH based drug delivery systems on various cells and offer novel information about these peptides