Enhanced anti-aging effect of nicotinamide mononucleotide encapsulated with reactive oxygen species responsive nanoparticles with liver and mitochondrial targeting abilities

Mitochondrial dysfunction is considered one of the characteristics of aging, related to cellular energy production, oxidative respiration, and the accumulation of excessive reactive oxygen species. In this study, liver and mitochondrial dual-targeting nanoparticles with ROS response were designed and prepared. They were based on the electrostatic interaction between lactobionic acid-modified sodium alginate and chitosan conjugated with SS31 using a thioketal linker for nicotinamide mononucleotide (NMN) delivery against senescence. The Pearson's correlation coefficient of NMN nanoparticles after a 4-hour incubation was found to be 0.9028. In vivo imaging of mice indicated liver accumulation after NMN nanoparticles treatment. These nanoparticles demonstrated the ability to restore senescence-related functions, liver homeostasis, and memory ability in mice. This restoration potentially involved cellular metabolism, mitochondrial function, nesting activity, and antioxidant capacity. Regarding the ROS responsive property analysis, an obvious release of ROS stimulus from NMN was observed at 10 mM H2O2. Senescence-related products (p21, lamin B1) were significantly ameliorated by NMN nanoparticles incubation. Furthermore, the NMN nanoparticles extended the lifespan, enhanced antioxidant capacity, and inhibited lipofuscin and ROS accumulation in Caenorhabditis elegans. These results suggested that NMN nanoparticles could prolong aging by reducing oxidative stress, providing a dual-targeting strategy with ROS response for treating senescence.