Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles

Abstract

Intracellular controlled release of molecules within senescent cells was achieved using mesoporous silica nanoparticles(MSNs) capped with a galacto-oligosaccharide (GOS) to contain the cargo molecules (magenta spheres; see scheme). The GOS is a substrate of the senescent biomarker, senescence-associated β-galactosidase (SA-β-gal), and releases the cargo upon entry into SA-β-gal expressing cells.

Link: http://1.usa.gov/TFDGVS 

Cell-penetrating superoxide dismutase attenuates oxidative stress-induced senescence by regulating the p53-p21Cip1 pathway and restores osteoblastic differentiation in human dental pulp stem cells

Abstract

Background

Human dental pulp stem cells (DPSCs) have potential applications in tissue regeneration because of their convenient cell harvesting procedures and multipotent capacity. However, the tissue regenerative potential of DPSCs is known to be negatively regulated by aging in long-term culture and under oxidative stress. With an aim of reducing cellular senescence and oxidative stress in DPSCs, an intracellular delivery system for superoxide dismutase 1 (SOD1) was developed. We conjugated SOD1 with a cell-penetrating peptide known as low-molecular weight protamine (LMWP), and investigated the effect of LMWP-SOD1 conjugates on hydrogen peroxide-induced cellular senescence and osteoblastic differentiation.

Results

LMWP-SOD1 significantly attenuated enlarged and flattened cell morphology and increased senescence-associated β-galactosidase activity. Under the same conditions, LMWP-SOD1 abolished activation of the cell cycle regulator proteins, p53 and p21^Cip1, induced by hydrogen peroxide. In addition, LMWP-SOD1 reversed the inhibition of osteoblastic differentiation and downregulation of osteogenic gene markers induced by hydrogen peroxide. However, LMWP-SOD1 could not reverse the decrease in odontogenesis caused by hydrogen peroxide.

Conclusion

Overall, cell-penetrating LMWP-SOD1 conjugates are effective for attenuation of cellular senescence and reversal of osteoblastic differentiation of DPSCs caused by oxidative stress inhibition. This result suggests potential application in the field of antiaging and tissue engineering to overcome the limitations of senescent stem cells.

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459692/

Picture: Ras-induced senescent IMR90

RED: Ras-induced senescent IMR90 (mCherry)

GREEN: Growing IMR90 (GFP)