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Start Over Author "Zhu, Xinyuan" Journal biomacromolecules
27 results on '"Zhu, Xinyuan"'

27. Iron Chelation Nanoparticles with Delayed Saturation as an Effective Therapy for Parkinson Disease.

Author

Wang N, Jin X, Guo D, Tong G, and Zhu X

Subjects
Animals, Behavior, Animal drug effects, Blood-Brain Barrier drug effects, Blood-Brain Barrier metabolism, Brain drug effects, Brain metabolism, Cell Survival drug effects, Disease Models, Animal, Humans, Iron Chelating Agents pharmacokinetics, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Nude, Nanoparticles chemistry, Neuroblastoma metabolism, Parkinson Disease metabolism, Phosphorylcholine analogs & derivatives, Phosphorylcholine chemistry, Polymethacrylic Acids chemistry, Tissue Distribution, Tumor Cells, Cultured, Iron metabolism, Iron Chelating Agents administration & dosage, Nanoparticles administration & dosage, Neuroblastoma drug therapy, Parkinson Disease drug therapy
Abstract

Iron accumulation in substantia nigra pars compacta (SNpc) has been proved to be a prominent pathophysiological feature of Parkinson's diseases (PD), which can induce the death of dopaminergic (DA) neurons, up-regulation of reactive oxygen species (ROS), and further loss of motor control. In recent years, iron chelation therapy has been demonstrated to be an effective treatment for PD, which has shown significant improvements in clinical trials. However, the current iron chelators are suboptimal due to their short circulation time, side effects, and lack of proper protection from chelation with ions in blood circulation. In this work, we designed and constructed iron chelation therapeutic nanoparticles protected by a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) to delay the saturation of iron chelators in blood circulation and prolong the in vivo lifetime, with HIV-1 trans-activating transcriptor (TAT) served as a shuttle to enhance the blood-brain barrier (BBB) permeability. We explored and investigated whether the Parkinsonian neurodegeneration and the corresponding symptoms in behaviors and physiologies could be prevented or reversed both in vitro and in vivo. The results demonstrated that iron chelator loaded therapeutic nanoparticles could reverse functional deficits in Parkinsonian mice not only physiologically but also behaviorally. On the contrary, both untreated PD mice and non-TAT anchored nanoparticle treated PD mice showed similar loss in DA neurons and difficulties in behaviors. Therefore, with protection of zwitterionic polymer and prolonged in vivo lifetime, iron chelator loaded nanoparticles with delayed saturation provide a PD phenotype reversion therapy and significantly improve the living quality of the Parkinsonian mice.

Published
2017
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