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.
Magnetic nanoparticles Fe3O4 doped by different amounts of Y3+ (0, 0.1, 1, 10 %) ions were designed to obtain maximum heating efficiency in magnetic hyperthermia for cancer treatment. Single phase formation was evident by XRD measurements. Improved magnetization value was obtained for the Fe3O4 sample with 1% of Y3+ doping. The specific absorption rate (SAR) and intrinsic loss of power (ILP) values for prepared colloids was obtained in water. The best results was estimated for Fe3O4 with 0.1% of Y3+ ions (SAR=194 W/g and ILP=1.85 nHm2/kg for magnetic field of 16kA/m with the frequency 413 kHz). The excellent biocompatibility with low cell cytotoxicity of Fe3O4:Y nanoparticles was observed. Immediately after magnetic hyperthermia treatment with Fe3O4:0.1%Y, the 4T1 cells viability decrease was observed (77% for 35 μg/ml, 68 % for 100 μg/ml). These results suggest that Fe3O4 doped by Y3+ ions nanoparticles are suitable for biomedical applications, especially for the hyperthermia treatment.