Fe-Cr-Nb-B Magnetic Particles and Adipose-Derived Mesenchymal Cells Trigger Cancer Cell Apoptosis by Magneto-Mechanical Actuation

Abstract

Magnetic nanoparticles (MPs) are emerging as powerful and versatile tools for biotechnology, including cancer research and theranostic applications. Stem cell-mediated magnetic particle delivery has been previously recognized as a modality to target sites of malignancies. Here, we propose the use of adipose-derived mesenchymal cells (ADSC) for the targeted delivery of Fe-Cr-Nb-B magnetic particles to human osteosarcoma (HOS) cells and magneto-mechanical actuation (MMA) for targeting and destroying HOS cells. We show that MPs are easily incorporated by ADSCs and HOS cells, as confirmed by TEM images and a ferrozine assay. MP-loaded ADSCs display increased motility towards tumor cells compared with their unloaded counterparts. MMA of MP-loaded ADSCs induces HOS destruction, as confirmed by the MTT and live/dead assays. MMA enables the release of the MPs towards cancer cells, producing a significant decrease (about 80%) in HOS viability immediately after application. In contrast, normal human dermal fibroblasts’ (NHDFs) viability exposed to similar conditions remains high, showing a differential behavior of normal and malignant cells to MP load and MMA exposure. Taken together, the method could derive successful strategies for in vivo applications in targeting and destroying malignant cells while protecting normal cells.

Synergistic Effect of Chemotherapy and Magnetomechanical Actuation of Fe-Cr-Nb-B Magnetic Particles on Cancer Cells

“…Our recent studies 6 showed that a concentration of 1 mg/mL of magnetic nanoparticles provided to cells was the most effective for magnetomechanical actuation. Considering the high amount of drug for both MTX and DOX of 7% w/w adsorbed on MPs, it was decided to reduce the dose of chemotherapeutic compound to 1 and 10 μg for each milligram of MPs.…”

“…The cellular uptake of nanomaterials is represented by several mechanisms such as endocytosis, phagocytosis, micropinocytosis, direct diffusion, and adhesive interactions. 26 Our recent studies 6 showed that a concentration of 1 mg/ mL of magnetic nanoparticles provided to cells was the most effective for magnetomechanical actuation. Considering the high amount of drug for both MTX and DOX of 7% w/w adsorbed on MPs, it was decided to reduce the dose of chemotherapeutic compound to 1 and 10 μg for each milligram of MPs.…”

“…Our group introduced Fe 68.2 Cr 11.5 Nb 0.3 B 20 nanoparticles produced by mechanical grinding in a high-ball energy mill of amorphous ribbon precursors with the same composition, previously obtained by rapid melt quenching. These MPs exhibit high anisotropy, parallelepipedic shape (with sizes ranging from 10 to 200 nm), amorphous structure, and ferromagnetic behavior and have shown promising results in reducing cancer cell viability under magnetomechanical actuation …”

“…These MPs exhibit high anisotropy, parallelepipedic shape (with sizes ranging from 10 to 200 nm), amorphous structure, and ferromagnetic behavior and have shown promising results in reducing cancer cell viability under magnetomechanical actuation. 6 …”

“…5 shown promising results in reducing cancer cell viability under magnetomechanical actuation. 6 The objective of this study is to develop a method for efficient cancer cell destruction through a synergistic approach, combining magnetomechanical actuation with clinically used antitumoral drugs. For our study, we used human osteosarcoma cells (HOS) as cancer cell representatives and adiposederived mesenchymal stem cells (ADSCs) as nontumoral representatives and possible carriers for MPs.…”