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

Abstract

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.

Potential of miRNA-Based Nanotherapeutics for Uveal Melanoma

“…To achieve promising preclinical results and evaluate the effectiveness of potential therapeutic miRNAs, selecting orthotopic tumor models that create a disease-relevant environment and using cells or tissues from patients with UM (also known as patient-derived xenografts, or PDX), are important. Performing experiments on PDX models that reflect the heterogeneity and diversity of clinical tumors may decrease the dissimilarities between human tumors and preclinical models [130]. Notably, primary UM spheroids retain the histological and genetic characteristics of the primary tumor, and the use of 3D spheroids has enabled early phase drug screening [139].…”

“…Nevertheless, NP surface modifications can improve delivery efficacy and biodistribution. For instance, studies have shown that the PEG-based (DSPE-PEG2000) coating in NPs avoids clearance and improves stability in the blood [129][130][131][132]. Moreover, conjugating the surfaces of NPs with a specific ligand can significantly increase the quantity of drug delivered to the location of interest, thereby avoiding normal tissues, enhancing the therapeutic efficiency and limiting the adverse effects of the drugs [77,130].…”

“…For instance, studies have shown that the PEG-based (DSPE-PEG2000) coating in NPs avoids clearance and improves stability in the blood [129][130][131][132]. Moreover, conjugating the surfaces of NPs with a specific ligand can significantly increase the quantity of drug delivered to the location of interest, thereby avoiding normal tissues, enhancing the therapeutic efficiency and limiting the adverse effects of the drugs [77,130]. In particular, UM cells strongly express the transmembrane glycoprotein intercellular adhesion molecule 1 (ICAM-1) and cell surface adhesion receptor CD44 [133].…”

Modulating undruggable targets to overcome cancer therapy resistance

“…As a consequence, some members of the family exhibit strong anti-proliferative effects, both in vitro and in vivo, associated with a cytotoxic activity while hydroxy tamoxifen shows only an anti-hormonal effect (Allard et al, 2008;Jaouen et al, 2015;Lainé et al, 2014). This is for example the case for P722 (54, Chart 9) which has been identified so far as the most cytotoxic member of the family, on MDA-MB231, triple negative breast cancer cells (IC50 = 35 nM) and to be highly cytotoxic also on several MDR cell lines (Idlas et al, 2021;Wang et al, 2019). ROS production observed with ferrocifens (Jaouen et al, 2015) make them potential candidates as agent capable of inducing ICD (Terenzi et al, 2016).…”

“…These molecules are lipophilic thus they can be in vivo administered only after formulation. It has been shown by Passirani and her group that lipid nanocapsules are a very well-suited formulation for this family of molecules (Idlas et al, 2021). These nanoparticles present a hybrid structure between polymer NPs and liposomes and are prepared by a solvent-free process.…”