Synchrotron Characterization of Hexagonal and Cubic Lipidic Phases Loaded with Azolate/Phosphane Gold(I) Compounds: A New Approach to the Uploading of Gold(I)-Based Drugs

Abstract

Gold(I) phosphane compounds have recently attracted a renewed interest as potential new protagonists in cancer therapy. A class of phosphane gold(I) complexes containing azolate ligands has been successfully tested against several cancer cell lines and, in particular, against basal-like breast (BLB) cancer, a form characterized by strongly severe diagnosis and short life lapse after classic chemotherapy. Even though the anticancer activity of gold(I) phosphane compounds is thoroughly ascertained, no study has been devoted to the possibility of their delivery in nanovectors. Herein, nonlamellar lyotropic liquid crystalline lipid nanosystems, a promising class of smart materials, have been used to encapsulate gold(I) azolate/phosphane complexes. In particular, ((triphenylphosphine)-gold(I)-(4,5-dichloroimidazolyl-1H-1yl)) (C-I) and ((triphenylphosphine)-gold(I)-(4,5-dicyanoimidazolyl-1H-1yl)) (C-II) have been encapsulated in three different lipid matrices: monoolein (GMO), phytantriol (PHYT) and dioleoyl-phosphatidylethanolamine (DOPE). An integrated experimental approach involving X-ray diffraction and UV resonant Raman (UVRR) spectroscopy, based on synchrotron light and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, has been employed to establish the effects of drug encapsulation on the structure and phase behavior of the host mesophases. The results indicate that gold(I) complexes C-I and C-II are successfully encapsulated in the three lipid matrices as evidenced by the drug-induced phase transitions or by the changes in the mesophase lattice parameters observed in X-ray diffraction experiments and by the spectral changes occurring in UV resonant Raman spectra upon loading the lipid matrices with C-I and C-II.

Gold Complexes in Anticancer Therapy: From New Design Principles to Particle‐Based Delivery Systems

“…Galassi and co-workers recently reported the encapsulation of (4,5-dichloroimidazolyl-1H-1yl) (triphenylphosphine)gold(I) (C-I, Figure 22a) and (4,5 dicyanoimidazolyl-1H-1yl) (triphenylphosphine)gold(I) (C-II, Figure 22a), in lyotropic liquid crystalline lipid NPs (P16) composed of three different building blocks (Figure 22b): Monoolein (GMO), phytantriol (PHYT) and dioleoyl phosphatidylethanolamine (DOPE). [280] C-I and C-II were successfully encapsulated in P16 formulations, as evidenced by the changes in the mesophase lattice parameters obtained from X-ray diffraction experiments, and by the spectral changes in the UV/Vis spectra of the gold complexes after loading, respectively. Since gold-phosphine complexes suffer from prompt ligand substitution reactions, their encapsulation is expected to enhance the stability and improve their therapeutic properties, [281][282][283] future work on in vitro and in vivo characterization of these types of nano-formulations will be of great interest.…”

“…Galassi and co‐workers recently reported the encapsulation of (4,5‐dichloroimidazolyl‐1H‐1yl) (triphenylphosphine)gold(I) ( C‐I , Figure 22a) and (4,5 dicyanoimidazolyl‐1H‐1yl) (triphenylphosphine)gold(I) ( C‐II , Figure 22a), in lyotropic liquid crystalline lipid NPs ( P16 ) composed of three different building blocks (Figure 22b): Monoolein (GMO), phytantriol (PHYT) and dioleoyl phosphatidylethanolamine (DOPE) [280] . C‐I and C‐II were successfully encapsulated in P16 formulations, as evidenced by the changes in the mesophase lattice parameters obtained from X‐ray diffraction experiments, and by the spectral changes in the UV/Vis spectra of the gold complexes after loading, respectively.…”

The structure–activity relationship of copper hydride nanoclusters in hydrogenation and reduction reactions

“…42,43 In Cu 6 -2 and Cu 6 -3 NCs, distinct vibrational bands around 1100 cm −1 were attributed to the C-P asymmetric stretching vibration. 44 The above results suggest that when phosphine ligands are coordinated to copper, the ligand backbone structures underwent no apparent changes.…”

Cubic and Hexagonal Mesophases for Protein Encapsulation: Structural Effects of Insulin Confinement

“…Lyotropic liquid crystalline (LLC) mesophases, particularly cubic and hexagonal ones, have been extensively studied as vehicles for molecules of different size and polarity such as small drugs, vitamins, peptides, proteins, and nucleic acids. − In fact, encapsulation permits the control of the release of the enclosed molecule in space and time, thus possibly allowing targeted therapies, and represents an efficient strategy for biomolecule stabilization. Recently, we reported the use of phytantriol (PHYT) or monoolein cubosomes for the loading and delivery of vitamin B12 and different anticancer compounds, namely, the commonly used 5-fluorouracil, , the plant extract isofuranodiene, and phosphane gold­(I) compounds, and demonstrated that encapsulation increased the drug stability and hence its anticancer activity. Bicontinuous cubic phases consist of a single, continuous bilayer draped over an infinite periodic minimal surface, subdividing space into two interpenetrating but unconnected water networks .…”