Evolution of Gold and Iron Oxide Nanoparticles in Conjugates with Methotrexate: Synthesis and Anticancer Effects

Abstract

Au and Fe nanoparticles and their conjugates with the drug methotrexate were obtained by an environmentally safe method of metal–vapor synthesis (MVS). The materials were characterized by transmission and scanning electron microscopy (TEM, SEM), X-ray photoelectron spectroscopy (XPS), and small-angle X-ray scattering using synchrotron radiation (SAXS). The use of acetone as an organic reagent in the MVS makes it possible to obtain Au and Fe particles with an average size of 8.3 and 1.8 nm, respectively, which was established by TEM. It was found that Au, both in the NPs and the composite with methotrexate, was in the Au0, Au+ and Au3+ states. The Au 4f spectra for Au-containing systems are very close. The effect of methotrexate was manifested in a slight decrease in the proportion of the Au0 state—from 0.81 to 0.76. In the Fe NPs, the main state is the Fe3+ state, and the Fe2+ state is also present in a small amount. The analysis of samples by SAXS registered highly heterogeneous populations of metal nanoparticles coexisting with a wide proportion of large aggregates, the number of which increased significantly in the presence of methotrexate. For Au conjugates with methotrexate, a very wide asymmetric fraction with sizes up to 60 nm and a maximum of ~4 nm has been registered. In the case of Fe, the main fraction consists of particles with a radius of 4.6 nm. The main fraction consists of aggregates up to 10 nm. The size of the aggregates varies in the range of 20–50 nm. In the presence of methotrexate, the number of aggregates increases. The cytotoxicity and anticancer activity of the obtained nanomaterials were determined by MTT and NR assays. Fe conjugates with methotrexate showed the highest toxicity against the lung adenocarcinoma cell line and Au nanoparticles loaded with methotrexate affected the human colon adenocarcinoma cell line. Both conjugates displayed lysosome-specific toxicity against the A549 cancer cell line after 120 h of culture. The obtained materials may be promising for the creation of improved agents for cancer treatment.

Bimetallic Gold–Iron Oxide Nanoparticles as Carriers of Methotrexate: Perspective Tools for Biomedical Applications

“…However, due to the absence of such bonds in MTX, it can be attributed to intermolecular interactions. At the same time, when interacting with active iron black, the relative intensity of this peak increased approximately three times, and only 1.5 times with less active gold black [29]. In the AuFe-MTX sample, the relative intensity of this peak is the same as in the spectrum of the Fe-MTX sample [29]; therefore, it may be preferentially assigned to the Fe-N bond.…”

“…X-ray photoelectron spectroscopy (XPS) can determine the characteristics of different chemical states of elements on the surface of a material. SAXS and XPS measurements and processing of experimental curves were carried out according to the method described in the paper by [29].…”

Nanocarriers for methotrexate delivery/codelivery in the frame of cancer diagnostics and treatment: a review

“…Anticancer activity based on MTT and NR assays was assessed. The results of Fe conjugates with MTX exhibited the highest toxicity as compared to MTX-loaded Au NPs against the lung adenocarcinoma cell line (Vasil'kov et al, 2023).…”

Tackling breast cancer with gold nanoparticles: twinning synthesis and particle engineering with efficacy

“… 241 The study of Alexander Vasil’kov with Au and iron-oxide NPs in conjugation with Methotrexate clearly suggested the better stability of AuNPs over iron-oxide NPs as iron was involved in oxidation at higher temperature. 242 Research for improvement of these limitations is ongoing and could be an interesting brainstorming option for future endeavours. Here, in this review, we would like to address the theranostic applications of AuNPs part by part, first its diagnostic applications, then therapeutic strategies including photothermal therapy, radiotherapy and AuNPs as cargo delivery.…”