1. Angiopep-Conjugated Nanoparticles for Targeted Long-Term Gene Therapy of Parkinson's Disease.
- Author
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Huang, Rongqin, Ma, Haojun, Guo, Yubo, Liu, Shuhuan, Kuang, Yuyang, Shao, Kun, Li, Jianfeng, Liu, Yang, Han, Liang, Huang, Shixian, An, Sai, Ye, Liya, Lou, Jinning, and Jiang, Chen
- Subjects
PARKINSON'S disease treatment ,BIOCONJUGATES ,TARGETED drug delivery ,PHYSIOLOGICAL effects of nanoparticles ,GENE therapy ,BLOOD-brain barrier - Abstract
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 H-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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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