Synthesis, Characterization, and In Vitro Cytotoxicity Evaluation of Doxorubicin-Loaded Magnetite Nanoparticles on Triple-Negative Breast Cancer Cell Lines

Abstract

In this study, we investigated the cytotoxicity of doxorubicin (DOX)-loaded magnetic nanofluids on 4T1 mouse tumor epithelial cells and MDA-MB-468 human triple-negative breast cancer (TNBC) cells. Superparamagnetic iron oxide nanoparticles were synthesized using sonochemical coprecipitation by applying electrohydraulic discharge treatment (EHD) in an automated chemical reactor, modified with citric acid and loaded with DOX. The resulting magnetic nanofluids exhibited strong magnetic properties and maintained sedimentation stability in physiological pH conditions. The obtained samples were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy, UV-spectrophotometry, dynamic light scattering (DLS), electrophoretic light scattering (ELS), vibrating sample magnetometry (VSM), and transmission electron microscopy (TEM). In vitro studies using the MTT method revealed a synergistic effect of the DOX-loaded citric-acid-modified magnetic nanoparticles on the inhibition of cancer cell growth and proliferation compared to treatment with pure DOX. The combination of the drug and magnetic nanosystem showed promising potential for targeted drug delivery, with the possibility of optimizing the dosage to reduce side-effects and enhance the cytotoxic effect on cancer cells. The nanoparticles’ cytotoxic effects were attributed to the generation of reactive oxygen species and the enhancement of DOX-induced apoptosis. The findings suggest a novel approach for enhancing the therapeutic efficacy of anticancer drugs and reducing their associated side-effects. Overall, the results demonstrate the potential of DOX-loaded citric-acid-modified magnetic nanoparticles as a promising strategy in tumor therapy, and provide insights into their synergistic effects.

Recent Progress and Challenges Regarding Magnetite-Based Nanoparticles for Targeted Drug Delivery

“…The experiments with human serum albumin solution indi-cated that the drug release was promoted by forming a protein corona-a protein coating on the surface of nanomaterials in biological fluids that improves biodistribution, biocompatibility, or cellular interactions. On the other hand, magnetite nanoparticles covered with citric acid (CA) were proposed as a potential DOX delivery system in the treatment of triple-negative breast cancer-an uncommon breast cancer subtype without an identified molecular target [54]. Citric acid is a popular surfactant, with one hydroxyl and three carboxyl functional groups, that stabilizes magnetite nanoparticles in aqueous suspensions.…”

The therapeutic potential of natural metabolites in targeting endocrine-independent HER-2-negative breast cancer

“…Next to clinically applied nanoforms of drugs new options are tested in pre-clinical and clinical setting (see below). Example of recently published pre-clinical study involves doxorubicin-loaded magnetite nanoparticles in TNBC in vitro cell line model ( Markhulia et al, 2023 ).…”

Advances in Doxorubicin-based nano-drug delivery system in triple negative breast cancer

“…Therefore, it has received wide concern from researchers. Markhulia et al ( Markhulia et al, 2023 ) synthesized a superparamagnetic iron oxide nanoparticles delivering DOX by chemical co-precipitation. The system maintains favorable sedimentation stability under physiological pH conditions, and DOX was rapidly released in the presence of ROS.…”