Targeted Brain Delivery of Rabies Virus Glycoprotein 29-Modified Deferoxamine-Loaded Nanoparticles Reverses Functional Deficits in Parkinsonian Mice

Linhao You, Jing Wang, Tianqing Liu, Yinlong Zhang, Xuexiang Han, Ting Wang, Shanshan Guo, Tianyu Dong, Junchao Xu, Gregory J. Anderson, Qiang Liu, Yan Zhong Chang, Xin Lou, Guangjun Nie

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Excess iron deposition in the brain often causes oxidative stress-related damage and necrosis of dopaminergic neurons in the substantia nigra and has been reported to be one of the major vulnerability factors in Parkinson's disease (PD). Iron chelation therapy using deferoxamine (DFO) may inhibit this nigrostriatal degeneration and prevent the progress of PD. However, DFO shows very short half-life in vivo and hardly penetrates the blood brain barrier (BBB). Hence, it is of great interest to develop DFO formulations for safe and efficient intracerebral drug delivery. Herein, we report a polymeric nanoparticle system modified with brain-targeting peptide rabies virus glycoprotein (RVG) 29 that can intracerebrally deliver DFO. The nanoparticle system penetrates the BBB possibly through specific receptor-mediated endocytosis triggered by the RVG29 peptide. Administration of these nanoparticles significantly decreased iron content and oxidative stress levels in the substantia nigra and striatum of PD mice and effectively reduced their dopaminergic neuron damage and as reversed their neurobehavioral deficits, without causing any overt adverse effects in the brain or other organs. This DFO-based nanoformulation holds great promise for delivery of DFO into the brain and for realizing iron chelation therapy in PD treatment.

Original languageEnglish (US)
Pages (from-to)4123-4139
Number of pages17
JournalACS Nano
Volume12
Issue number5
DOIs
StatePublished - May 22 2018

Keywords

  • Parkinson's disease
  • blood brain barrier
  • deferoxamine
  • polymeric nanoparticles
  • rabies virus glycoprotein 29

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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