Harnessing Nanotechnology for Cellular Health through Strategic Modulation and Nanoscale Control of Electron Mobility

Excessive oxidative stress in human cells is linked to aging and underpins pathologies such as Alzheimer's disease, diabetes, and cancer. Understanding the molecular mechanisms behind this is crucial, and to this end, cell models that can produce varying levels of oxidative stress are essential. This work has achieved this by creating a library of gold nanoparticles (GNPs) with diverse ferrocene-containing ligands and incorporating them into human cells in nontoxic doses. These GNPs create cell models with different levels of oxidative stress. The roles of these ligands in controlling oxidative stress were elucidated through first-principles calculations. It was found that substituents covalently adjacent to the ferrocene in the ligand significantly influence electron mobility within the ferrocene group, thereby playing a predominant role (75.6%) in modulating the redox activity of the GNPs. In contrast, the presence of distal substituents, which are not directly bonded to ferrocene, was found to have a lesser (24.4%) yet noteworthy impact on this activity through intramolecular interactions adjusting atomic charge redistribution. This mechanistic understanding of how nanostructures control cellular redox activities enriches our knowledge of nanobio interactions. It also introduces advanced methods for precisely regulating cellular oxidative stress levels and represents a significant advancement in leveraging nanotechnology for targeted redox therapies.