Anti-amyloid activity of amino acid functionalized magnetic nanoparticles on αLactalbumin aggregation

Abstract

Protein amyloid aggregation involves structural changes in native protein conformers and the formation of amyloid fibrils that accumulate in deposits in the human body. This study explores the effect of magnetic nanoparticles functionalized with amino acids (aaMNPs)—cysteine (Cys), poly-L-lysine (PLL), or proline (Pro)—on the amyloid aggregation of α-lactalbumin (αLA) and its amyloid fibrils (LAF). Our results from thioflavin T fluorescence assay (ThT), atomic force microscopy (AFM), and infrared spectroscopy revealed that the studied aaMNPs inhibit αLA fibrillization and destruct LAF in a concentration-dependent manner. The type of amino acid used for nanoparticle functionalization significantly influences the anti-amyloid efficacy. ProMNPs exhibit the highest inhibitory activity, with the timing of their addition being crucial Conversely, CysMNPs demonstrate the highest destructing activity. AFM image analysis through grain mapping was employed to quantify the anti-amyloid effects of aaMNPs. Cytotoxicity testing on kidney cells identified PLLMNPs as the only cytotoxic nanoparticles in our study. These findings clarify the mechanisms of inhibition and destruction of LAF in the presence of aaMNPs, which could inform the design of nanoparticles for therapeutic purposes in the future.