Fixation screws and other temporary magnesium alloy fixation devices are used in orthopedic practice because of their biodegradability, biocompatibility and acceptable biodegradation rates. The substitution of dissolving implant by tissues during the healing process is one of the main requirements for biodegradable implants. Previously, clinical tests showed the effectiveness of Ga ions on bone tissue regeneration. This work is the first systematic study on the corrosion rate and biocompatibility of Mg–Zn–Ga–(Y) alloys prepared by hot extrusion, where Ga is an additional major alloying element, efficient as a bone-resorption inhibitor. Most investigated alloys have a low corrosion rate in Hanks’ solution close to ~0.2 mm/year. No cytotoxic effects of Mg–2Zn–2Ga (wt.%) alloy on MG63 cells were observed. Thus, considering the high corrosion resistance and good biocompatibility, the Mg–2Zn–2Ga alloy is possible for applications in osteosynthesis implants with improved bone tissue regeneration ability.
Redox-responsive and magnetic nanomaterials are widely used in tumor treatment separately, and while the application of their combined functionalities is perspective, exactly how such synergistic effects can be implemented is still unclear. This report investigates the internalization dynamics of magnetic redox-responsive nanoparticles (MNP-SS) and their cytotoxicity toward PC-3 and 4T1 cell lines. It is shown that MNP-SS synthesized by covalent grafting of polyethylene glycol (PEG) on the magnetic nanoparticle (MNP) surface via SS-bonds lose their colloidal stability and aggregate fully in a solution containing DTT, and partially in conditioned media, whereas the PEGylated MNP (MNP-PEG) without S-S linker control remains stable under the same conditions. Internalized MNP-SS lose the PEG shell more quickly, causing enhanced magnetic core dissolution and thus increased toxicity. This was confirmed by fluorescence microscopy using MNP-SS dual-labeled by Cy3 via labile disulfide, and Cy5 via a rigid linker. The dyes demonstrated a significant difference in fluorescence dynamics and intensity. Additionally, MNP-SS demonstrate quicker cellular uptake compared to MNP-PEG, as confirmed by TEM analysis. The combination of disulfide bonds, leading to faster dissolution of the iron oxide core, and the high-oxidative potential Fe3+ ions can synergically enhance oxidative stress in comparison with more stable coating without SS-bonds in the case of MNP-PEG. It decreases the cancer cell viability, especially for the 4T1, which is known for being sensitive to ferroptosis-triggering factors. In this work, we have shown the effect of redox-responsive grafting of the MNP surface as a key factor affecting MNP-internalization rate and dissolution with the release of iron ions inside cancer cells. This kind of synergistic effect is described for the first time and can be used not only in combination with drug delivery, but also in treatment of tumors responsive to ferroptosis.
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