Combating Atherosclerosis with Chirality/Phase Dual-Engineered Nanozyme Featuring Microenvironment-Programmed...

Area of Science:

• Biomaterials Science
• Aging Research
• Nanotechnology

Background:

• Cellular senescence is a key factor in aging and disease development.
• Existing anti-aging therapies have limitations.
• Novel approaches are needed to target senescence effectively.

Purpose of the Study:

• To develop and characterize a high-entropy alloy (HEA)-based nanozyme for combating cellular senescence.
• To investigate the catalytic activity and anti-aging therapeutic function of the nanozyme.
• To explore the underlying mechanisms of the nanozyme's senolytic action and its potential in treating age-related diseases.

Main Methods:

• Fabrication and characterization of an amorphous HEA-based nanozyme.
• Assessment of nanozyme catalytic activity (peroxide and superoxide dismutase) under normal and aging conditions.
• Validation of chiral-dependent senolytic performance using D-handed PtPd2CuFe in aging models.
• Multi-Omics analyses to elucidate the mechanism of action.
• Evaluation of concentration-dependent anti-aging effects and senomorphic potential.

Main Results:

• The nanozyme exhibits crucial peroxide and superoxide dismutase (SOD) activity for its anti-aging function.
• D-handed PtPd2CuFe demonstrated significant senolytic performance across various aging models.
• Multi-Omics data revealed nanozyme-induced disruption of iron-thiol clusters and induction of cuproptosis and ferroptosis in senescent cells.
• The nanozyme showed concentration-dependent anti-aging effects, acting as a senomorphic even at ultralow doses.
• The D-handed PtPd2CuFe nanozyme proved effective in managing atherosclerosis, a disease involving senescent cells.

Conclusions:

• The developed HEA-based nanozyme, particularly D-handed PtPd2CuFe, is a promising therapeutic agent against cellular senescence.
• The nanozyme's mechanism involves restoring mitochondrial function and preventing ferroptosis/cuproptosis.
• Its dual senolytic and senomorphic properties offer versatile therapeutic potential for age-related diseases, including atherosclerosis.