生物质碳点通过抑制铁死亡和氧化应激减轻帕金森病神经元凋亡

Abstract

Dragon fruit -derived carbon dots (DFCDs) are successfully synthesized with ligand-free BBB penetration and high biosafety. • Direct mitigation of neuronal apoptosis is achieved via downstream ROS scavenging. • DFCDs initiate biological inhibition of ferroptosis to prevent secondary apoptosis. • This strategy aids in the synergistic in vivo therapeutic efficacy and motor recovery of Parkinson's disease. The therapeutic landscape for Parkinson's disease (PD) is fraught with challenges, primarily due to the intertwined pathogenic cycles of oxidative stress and ferroptosis that perpetuate neuronal loss. While conventional antioxidants fail to address the iron-mediated root of reactive oxygen species (ROS) generation, existing ferroptosis inhibitors suffer from poor blood-brain barrier (BBB) permeability, rely on physical chelation and lack intrinsic ROS-scavenging ability. Here, we report the one-pot synthesis of bifunctional carbon dots (DFCDs) from dragon fruit, a sustainable biomass, as a novel nanotherapeutic agent that concurrently disrupts both pathways. Distinct from conventional strategies that rely on physical iron chelation, the DFCDs exhibit a unique dual functionality: they possess potent antioxidant activity to neutralize downstream ROS and, most notably, function as endogenous pathway modulators that inhibit ferroptosis by upregulating the endogenous cytoprotective SLC7A11/GPX4 axis. Their ultrasmall size (~4.1 nm) facilitates exceptional BBB penetration without requiring complex surface functionalization. In a murine PD model, DFCDs administration significantly mitigates neuroinflammation, reduces dopaminergic neuron degeneration, and suppresses ferroptosis, culminating in the substantial restoration of motor functions. This work pioneers the use of biologically-active carbon dots as a standalone therapeutic and presents a simplified, biomass-derived strategy offering a potent and translatable approach for synergistic PD treatment.