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Ultra-small polydopamine nanomedicine-enabled antioxidation against senescence
Jiamei Han1, Jiao Wang1, Hongwei Shi1
1School of Life Sciences, Shanghai University, Shanghai, China.
Abstract:
Senescence is a cellular response characterized by cells irreversibly stopping dividing and entering a state of permanent growth arrest. One of the underlying pathophysiological causes of senescence is the oxidative stress-induced damage, indicating that eliminating the reactive oxygen and nitrogen species (RONS) may be beneficial to prevent and/or alleviate senescence. Herein, we developed ultra-small polydopamine nanoparticles (UPDA NPs) with superoxide dismutase (SOD)/catalase (CAT) enzyme-mimic activities, featuring broad-spectrum RONS-scavenging capability for inducing cytoprotective effects against RONS-mediated damage. The engineered UPDA NPs can restore senescence-related renal function, tissue homeostasis, fur density, and motor ability in mice, potentially associated with the regulation of multiple genes involved in lipid metabolism, mitochondrial function, energy homeostasis, telomerase activity, neuroprotection, and inflammatory responses. Importantly, the dietary UPDA NPs can enhance the antioxidant capacity, improve the climbing ability, and prolong the lifespan of Drosophila. Notably, UPDA NPs possess excellent biocompatibility stemming from the ultra-small size, ensuring quick clearance out of the body. These findings reveal that UPDA NPs can delay aging through reducing oxidative stress and provide a paradigm and practical strategy for treating senescence and senescence-related diseases.
Insights
Ultra-small polydopamine nanoparticles (UPDA NPs) with enzyme-mimic activities scavenge reactive oxygen and nitrogen species (RONS) to combat cellular senescence. These nanoparticles restore age-related functions and extend lifespan, offering a novel anti-aging strategy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Gerontology
Background:
- Cellular senescence, a state of irreversible growth arrest, is linked to aging and age-related diseases.
- Oxidative stress, caused by reactive oxygen and nitrogen species (RONS), is a key driver of senescence.
- Current strategies for managing senescence often lack efficacy or have side effects.
Purpose of the Study:
- To develop and evaluate ultra-small polydopamine nanoparticles (UPDA NPs) with enhanced RONS-scavenging capabilities.
- To investigate the potential of UPDA NPs in preventing and alleviating senescence.
- To explore the therapeutic effects of UPDA NPs on age-related decline in vivo.
Main Methods:
- Engineered ultra-small polydopamine nanoparticles (UPDA NPs) with superoxide dismutase (SOD) and catalase (CAT) enzyme-mimic activities.
- Assessed broad-spectrum RONS-scavenging capacity and cytoprotective effects of UPDA NPs.
- Evaluated the efficacy of UPDA NPs in restoring senescence-related phenotypes in mice and Drosophila models.
Main Results:
- UPDA NPs demonstrated potent RONS-scavenging and cytoprotective effects.
- UPDA NPs treatment restored renal function, tissue homeostasis, fur density, and motor ability in mice.
- UPDA NPs enhanced antioxidant capacity, improved climbing ability, and prolonged lifespan in Drosophila.
Conclusions:
- UPDA NPs effectively delay aging by reducing oxidative stress and mitigating senescence.
- These nanoparticles show promise as a therapeutic strategy for senescence and related diseases.
- The ultra-small size ensures excellent biocompatibility and rapid clearance, minimizing potential toxicity.
