Ferrocifen Loaded Lipid Nanocapsules: A Promising Anticancer Medication against Multidrug Resistant Tumors

Simple Summary One of the primary causes of chemotherapy failure is the occurrence of cancer multidrug resistance (MDR). Uncontrolled growth of resistant tumor cells leads to metastasis and recurrence, associated with high mortalities. Ferrocifens have been shown to possess anticancer properties via an original mechanism dependent on redox properties and generation of active metabolites that can cause disruption of cell metabolism. However, these molecules are highly insoluble in water, requiring a formulation stage before being administered in vivo. Lipid nanocapsules (LNCs) have already demonstrated their ability to successfully encapsulate various hydrophobic therapeutic agents, such as ferrocifens, and offer the option of surface modification, making it possible to adapt the pharmacological behavior of the nanocarrier. The aim of this review is to give, for the first time, an overview of the in vitro and in vivo studies performed with ferrocifen-loaded LNCs on several MDR cancers. Resistance of cancer cells to current chemotherapeutic drugs has obliged the scientific community to seek innovative compounds. Ferrocifens, lipophilic organometallic compounds composed of a tamoxifen scaffold covalently bound to a ferrocene moiety, have shown very interesting antiproliferative, cytotoxic and immunologic effects. The formation of ferrocenyl quinone methide plays a crucial role in the multifaceted activity of ferrocifens. Lipid nanocapsules (LNCs), meanwhile, are nanoparticles obtained by a free organic solvent process. LNCs consist of an oily core surrounded by amphiphilic surfactants and are perfectly adapted to encapsulate these hydrophobic compounds. The different in vitro and in vivo experiments performed with this ferrocifen-loaded nanocarrier have revealed promising results in several multidrug-resistant cancer cell lines such as glioblastoma, breast cancer and metastatic melanoma, alone or in combination with other therapies. This review provides an exhaustive summary of the use of ferrocifen-loaded LNCs as a promising nanomedicine, outlining the ferrocifen mechanisms of action on cancer cells, the nanocarrier formulation process and the in vivo results obtained over the last two decades.