Cellular senescence may contribute to aging and age-related diseases and senolytic drugs that selectively kill senescent cells may delay aging and promote healthspan. More recently, several categories of senolytics have been established, namely HSP90 inhibitors, Bcl-2 family inhibitors and natural compounds such as quercetin and fisetin. However, senolytic and senostatic potential of nanoparticles and surface-modified nanoparticles has never been addressed. In the present study, quercetin surface functionalized Fe3O4 nanoparticles (MNPQ) were synthesized and their senolytic and senostatic activity was evaluated during oxidative stress-induced senescence in human fibroblasts in vitro. MNPQ promoted AMPK activity that was accompanied by non-apoptotic cell death and decreased number of stress-induced senescent cells (senolytic action) and the suppression of senescence-associated proinflammatory response (decreased levels of secreted IL-8 and IFN-β, senostatic action). In summary, we have shown for the first time that MNPQ may be considered as promising candidates for senolytic- and senostatic-based anti-aging therapies.

The PRHD@MnFe2O4 binary hybrids have shown a potential for applications in the biomedical field. The polymer cover/shell provides sufficient surface protection of magnetic nanoparticles against adverse effects on the biological systems, e.g., it protects against Fenton’s reactions and the generation of highly toxic radicals. The heating ability of the PRHD@MnFe2O4 was measured as a laser optical density (LOD) dependence either for powders as well as nanohybrid dispersions. Dry hybrids exposed to the action of NIR radiation (808 nm) can effectively convert energy into heat that led to the enormous temperature increase ΔT 170 °C (>190 °C). High concentrated colloidal suspensions (5 mg/mL) can generate ΔT of 42 °C (65 °C). Further optimization of the nanohybrids amount and laser parameters provides the possibility of temperature control within a biologically relevant range. Biological interactions of PRHD@MnFe2O4 hybrids were tested using three specific cell lines: macrophages (RAW 264.7), osteosarcoma cells line (UMR-106), and stromal progenitor cells of adipose tissue (ASCs). It was shown that the cell response was strongly dependent on hybrid concentration. Antimicrobial activity of the proposed composites against Escherichia coli and Staphylococcus aureus was confirmed, showing potential in the exploitation of the fabricated materials in this field.

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Magnetite nanoparticles (MNPs) were synthesized using two distinctly different approaches, co-precipitation (CP) and thermal decomposition (TD), and further surface functionalized with organophosphonic ligands containing different numbers of phosphonic groups. We have shown that it is possible to fabricate flower-like assemblies of MNPs through TD at lower temperatures, whereas CP MNPs formed agglomerates of particles with broad size distribution and irregular shapes. The effect of the organophosphonic ligands on the heating efficiency of the TD and CP MNPs under dual mode stimulation (simultaneous action of AMF and NIR laser radiation) was studied for the first time. It was found that in the case of the cost-effective CP MNP synthesis surface functionalization with chosen phosphonic ligands leads to higher heating efficiency upon laser stimulation, whereas better performance of TD MNPs was found under the action of AMF due to the significant difference of nanoparticle properties. The biocompatibility of surface functionalized MNPs with organophosphonic ligands was evaluated through thorough studies of the metabolic activity of MNPs in normal human foreskin fibroblasts as well as oxidative stress induction and oxidation stress response which has not been previously reported for most of the organophosphonic moieties used in this study.

Osteoporosis is characterized by the reduction of bone mineral density and the weakness of the bone strength leading to fractures. Searching for new compounds that stimulate bone activity and their ability to reconstruct seems to be a promising tool in osteoporosis treatment. Here, we performed analyses comparing the impact of polyrhodanine (PRHD) and its derivatives on the viability (anti-proliferative tests), morphology and mitochondrial network (confocal microscopy) towards pre-osteoblasts (MC3T3-E1 cell line) and osteoclasts (4B12 cell line). Moreover, we assessed the expression of genes associated with the apoptosis, inflammation and osteogenic differentiation by qPCR technique. Our results clearly demonstrated that PRHD and its modification at ratio 10/90 significantly improves the pre-osteoblast’s proliferative abilities, while reducing osteoclast function. The observed effects were strongly correlated with the cytoskeleton and mitochondrial network development and arrangement. Additionally, the expression profile of genes revealed enhanced apoptosis of osteoclasts in the case of PRHD and its modification at ratio 10/90. Moreover, in this case we also observed strong anti-inflammatory properties demonstrated by decreased expression of Il1b, Tnfa and Tgfb in pre-osteoblasts and osteoclasts. On the other hand, enhanced expression of the markers associated with bone remodeling, namely, osteopontin (OPN), osteocalcin (OCL) and alkaline phosphatase (ALP), seem to confirm the role of PRHD@MnFe2O4 in the promotion of differentiation of pre-osteoblasts through the ALP-OPN-OCL axis. Based on these observations, PRHD@MnFe2O4 could be a potential agent in osteoporosis treatment in future, however, further studies are still required.