Rational design, synthesis and evaluation of mitoxantrone conjugated with mutated Gonadotropin Releasing Hormone (GnRH) for the treatment of hormone-dependent cancer

Gonadotropin-releasing hormone (GnRH) or luteinizing hormone-releasing hormone (LHRH), has a significant role in fertility by initiating the regulation of gonadal axial, (1, 2).Several GnRH peptide analogues have been clinically used for the treatment not only to address fertility issues but also to treat hormone-dependent cancers, as GnRH receptors (GnRHR) are overexpressed in cancer cells.A promising strategy for selective immunosuppression of cancer cells, includes the development of delivery systems based on GnRH analogues conjugated with anti-cancer drugs to target the GnRHR on cancer cells (3).This targeted approach is advantageous due to the higher expression of GnRH receptors compared to healthy cells, allowing for more precise and effective treatment (2).In this study, we designed a modified mitoxantrone molecule (immunosuppressing agent) conjugated with an altered GnRH peptide via a disulfide bond (3).This conjugation aims to facilitate the in situ release of mitoxantrone through the reduction of the disulfide bond by the thioredoxin system.