Angiopep-conjugated nanoparticles for targeted long-term gene therapy of parkinson's disease

Rongqin Huang, Haojun Ma, Yubo Guo, Shuhuan Liu, Yuyang Kuang, Kun Shao, Jianfeng Li, Yang Liu, Liang Han, Shixian Huang, Sai An, Liya Ye, Jinning Lou, Chen Jiang

Research output: Contribution to journalArticlepeer-review


Purpose: To prepare an angiopep-conjugated dendrigraft poly-L-lysine (DGL)-based gene delivery system and evaluate the neuroprotective effects in the rotenone-induced chronic model of Parkinson's disease (PD). Methods: Angiopep was applied as a ligand specifically binding to low-density lipoprotein receptor-related protein (LRP) which is overexpressed on blood-brain barrier (BBB), and conjugated to biodegradable DGL via hydrophilic polyethyleneglycol (PEG), yielding DGL-PEG-angiopep (DPA). In vitro characterization was carried out. The neuroprotective effects were evaluated in a chronic parkinsonian model induced by rotenone using a regimen of multiple dosing intravenous administrations. Results: The successful synthesis of DPA was demonstrated via 1H-NMR. After encapsulating the therapeutic gene encoding human glial cell line-derived neurotrophic factor (hGDNF), DPA/hGDNF NPs showed a sphere-like shape with the size of 119 ± 12 nm and zeta potential of 8.2 ± 0.7 mV. Angiopep-conjugated NPs exhibited higher cellular uptake and gene expression in brain cells compared to unmodified counterpart. The pharmacodynamic results showed that rats in the group with five injections of DPA/hGDNF NPs obtained best improved locomotor activity and apparent recovery of dopaminergic neurons compared to those in other groups. Conclusion: This work provides a practical non-viral gene vector for long-term gene therapy of chronic neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)2549-2559
Number of pages11
JournalPharmaceutical Research
Issue number10
StatePublished - Oct 2013
Externally publishedYes


  • Parkinson's disease
  • angiopep-conjugated nanoparticles
  • dendrigraft poly-L-lysine
  • gene therapy
  • multiple dosing administrations

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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