The misfolding and aggregation ofα-synuclein(α-syn)is closely associated with Parkinson’s disease(PD).Here,chiral dimanganese trioxide(Mn_(2)O_(3))nanoparticles(NPs)were prepared for PD treatment enhanced by a noni...The misfolding and aggregation ofα-synuclein(α-syn)is closely associated with Parkinson’s disease(PD).Here,chiral dimanganese trioxide(Mn_(2)O_(3))nanoparticles(NPs)were prepared for PD treatment enhanced by a noninvasive electromagnetic field(MF).The affinity constants of D-NPs towardα-syn monomer(mono)orα-syn fibril were 3.5 times or 5.2 times higher,respectively,than those of L-NPs,and the mechanical force generated by NPs under a MF further promoted the interaction between NPs andα-syn to amplify the difference between L-NPs and D-NPs.As the synergy effect of the preferentially affinity ability and MF-induced mechanical forces,D-NPs exhibited a better inhibitory efficiency onα-syn fibrillization than L-NPs.Furthermore,after differentially cellular uptake of L-/D-NPs via the caveolin-mediated pathway,as reactive oxygen species(ROS)-scavengers,D-NPs possess higher efficiency in decreasing intracellular ROS level than L-NPs to provide higher cytoprotective efficiency to neuron cells.In vivo data showed that after treatment with D-NPs under a MF for 60 days,α-syn concentration in the cerebrospinal fluid of PD mice decreased 81%,while dopamine level in the brain of PD mice increased 2.3-fold.These findings indicated the potential of utilizing the synergic interplay of chiral NPs and MF for treating disease and opened a new path to explore the nanoscale chirality for regulating the biological effect.展开更多
基金supported by the National Natural Science Foundation of China (32071400,51902136)
文摘The misfolding and aggregation ofα-synuclein(α-syn)is closely associated with Parkinson’s disease(PD).Here,chiral dimanganese trioxide(Mn_(2)O_(3))nanoparticles(NPs)were prepared for PD treatment enhanced by a noninvasive electromagnetic field(MF).The affinity constants of D-NPs towardα-syn monomer(mono)orα-syn fibril were 3.5 times or 5.2 times higher,respectively,than those of L-NPs,and the mechanical force generated by NPs under a MF further promoted the interaction between NPs andα-syn to amplify the difference between L-NPs and D-NPs.As the synergy effect of the preferentially affinity ability and MF-induced mechanical forces,D-NPs exhibited a better inhibitory efficiency onα-syn fibrillization than L-NPs.Furthermore,after differentially cellular uptake of L-/D-NPs via the caveolin-mediated pathway,as reactive oxygen species(ROS)-scavengers,D-NPs possess higher efficiency in decreasing intracellular ROS level than L-NPs to provide higher cytoprotective efficiency to neuron cells.In vivo data showed that after treatment with D-NPs under a MF for 60 days,α-syn concentration in the cerebrospinal fluid of PD mice decreased 81%,while dopamine level in the brain of PD mice increased 2.3-fold.These findings indicated the potential of utilizing the synergic interplay of chiral NPs and MF for treating disease and opened a new path to explore the nanoscale chirality for regulating the biological effect.
