Investigating the Interaction of an Anticancer Nucleolipidic Ru(III) Complex with Human Serum Proteins: A Spectroscopic Study

Abstract

Ruthenium(III) complexes are very promising candidates as metal-based anticancer drugs, and several studies have supported the likely role of human serum proteins in the transport and selective delivery of Ru(III)-based compounds to tumor cells. Herein, the anticancer nanosystem composed of an amphiphilic nucleolipid incorporating a Ru(III) complex, which we named DoHuRu, embedded into the biocompatible cationic lipid DOTAP, was investigated as to its interaction with two human serum proteins thought to be involved in the mechanism of action of Ru(III)-based anticancer drugs, i.e., human serum albumin (HSA) and human transferrin (hTf). This nanosystem was studied in comparison with the simple Ru(III) complex named AziRu, a low molecular weight metal complex previously designed as an analogue of NAMI-A, decorated with the same ruthenium ligands as DoHuRu but devoid of the nucleolipid scaffold and not inserted in liposomal formulations. For this study, different spectroscopic techniques, i.e., Fluorescence Spectroscopy and Circular Dichroism (CD), were exploited, showing that DoHuRu/DOTAP liposomes can interact with both serum proteins without affecting their secondary structures.

Design, Synthesis, and Characterization of an Amphiphilic Lipoic Acid-Based Ru(III) Complex as a Versatile Tool for the Functionalization of Different Nanosystems

“…In this context, starting from a structurally-related NAMI-A analog, called AziRu (Figure 1a) [36,37], we previously designed and synthesized a library of highly functionalized nucleolipid- [29,38] or aminoacyl lipid-based [39] Ru(III)-containing complexes. The resulting derivatives have been then co-formulated with biocompatible vesicle-forming Molecules 2023, 28, 5775 2 of 12 lipids, such as POPC or DOTAP, obtaining a mini-library of various Ru(III)-loaded liposomes [29,36,40,41] characterized by high antiproliferative activity on human cancer cells, especially of breast cancer origin, and no relevant toxicity on control healthy cell lines [29,42]. These liposomes also proved to be effective and selective in vivo in preclinical evaluation studies in suitable breast cancer xenografts mouse models [43,44].…”