Synthesis and Anti-Melanoma Activity of L-Cysteine-Coated Iron Oxide Nanoparticles Loaded with Doxorubicin

• Published in: Nanomaterials (Basel, Switzerland) Switzerland), 2023-02, Vol.13 (4), p.621
• Main Authors: Toderascu, Luiza Izabela, Sima, Livia Elena, Orobeti, Stefana, Florian, Paula Ecaterina, Icriverzi, Madalina, Maraloiu, Valentin-Adrian, Comanescu, Cezar, Iacob, Nicusor, Kuncser, Victor, Antohe, Iulia, Popescu-Pelin, Gianina, Stanciu, George, Ionita, Petre, Mihailescu, Cristian N, Socol, Gabriel
• Format: Article
• Language: English
• Subjects: Amino acids; Ammonia; Analysis; Apoptosis; Aqueous solutions; Biocompatibility; Cancer therapies; Cell cycle; Cell lines; Chemical synthesis; chemotherapeutic; Chemotherapy; Cysteine; Diffraction; Dox; Doxorubicin; Drug delivery; Ethanol; Fiber optics; Fourier transform infrared spectroscopy; Gold; Internalization; Iron oxides; L-Cys; magnetic nanoparticles; Magnetic properties; MAP kinase; Melanoma; Metastases; Methods; Mossbauer spectroscopy; Mössbauer spectroscopy; Nanoparticles; Properties; Radiation; Signal transduction; Skin cancer; Spectrum analysis; Superconducting quantum interference devices; Synthesis; Transmission electron microscopy; Tumors; X-rays
• ISSN: 2079-4991; 2079-4991
• DOI: 10.3390/nano13040621

In this study, we report on the synthesis of L-Cysteine (L-Cys)-coated magnetic iron oxide nanoparticles (NPs) loaded with doxorubicin (Dox). The Fe O -L-Cys-Dox NPs were extensively characterized for their compositional and morpho-structural features using EDS, SAED, XRD, FTIR and TEM. XPS, Mӧssbauer spectroscopy and SQUID measurements were also performed to determine the electronic and magnetic properties of the Fe O -L-Cys-Dox nanoparticles. Moreover, by means of a FO-SPR sensor, we evidenced and confirmed the binding of Dox to L-Cys. Biological tests on mouse (B16F10) and human (A375) metastatic melanoma cells evidenced the internalization of magnetic nanoparticles delivering Dox. Half maximum inhibitory concentration IC50 values of Fe O -L-Cys-Dox were determined for both cell lines: 4.26 µg/mL for A375 and 2.74 µg/mL for B16F10, as compared to 60.74 and 98.75 µg/mL, respectively, for unloaded controls. Incubation of cells with Fe O -L-Cys-Dox modulated MAPK signaling pathway activity 3 h post-treatment and produced cell cycle arrest and increased apoptosis by 48 h. We show that within the first 2 h of incubation in physiological (pH = 7.4) media, ~10-15 µM Dox/h was released from a 200 µg/mL Fe O -L-Cys-Dox solution, as compared to double upon incubation in citrate solution (pH = 3), which resembles acidic environment conditions. Our results highlight the potential of Fe O -L-Cys-Dox NPs as efficient drug delivery vehicles in melanoma therapy.