Conformational modulation and inhibition of lysozyme amyloid fibrillation by lanthanum-doped red carbon dots: a multispectroscopic, morphological, and molecular simulation study.

This study investigates the molecular interactions between rare-earth-doped carbon nanomaterials and amyloidogenic proteins. Red-emitting lanthanum-doped carbon dots (La-CDs) were synthesized via a one-pot hydrothermal method, exhibiting strong fluorescence at 603 nm, an absolute quantum yield of 23.57%, and excellent optical stability. Using an integrated approach combining multispectroscopic techniques, thermodynamics, molecular docking, and molecular dynamics simulations, we systematically investigated the binding of La-CDs to hen egg white lysozyme (HEWL). La-CDs bind specifically to a non-catalytic surface pocket distant from the catalytic center with moderate affinity (∼ 104 L·mol-1), driven primarily by hydrogen bonding and van der Waals interactions. Thermodynamic analysis revealed a spontaneous and enthalpy-driven process (ΔH = -33.33 kJ·mol-1; ΔG = -25.83 kJ·mol-1 at 298 K). Binding increased α-helical content (29.8% to 32.1%) and decreased β-sheet content (22.2% to 18.9%), accompanied by a 61.3% reduction in denaturation enthalpy without altering the melting temperature. Functionally, La-CDs effectively inhibited HEWL amyloid fibril formation, prolonging the nucleation lag phase, reducing the elongation rate, and lowering final fibril yield by 19.79%. This inhibitory effect, along with the disassembly of pre-formed mature fibrils, was morphologically validated by transmission electron microscopy. Furthermore, La-CDs demonstrated low cytotoxicity against HepG2 cells (viability >80% at 100 μg·mL-1) and enabled intracellular red fluorescence imaging, with preferential mitochondrial accumulation confirmed by co-localization studies. Notably, La-CDs exhibited effective cytoprotection by rescuing HepG2 cells from HEWL fibril-induced toxicity. These findings advance fundamental understanding of nanomaterial-protein interfacial behavior and establish La-CDs as promising conformational modulators for anti-amyloid therapeutics.