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Chitosan‐based gene delivery vectors targeted to the peripheral nervous system
Author(s) -
Oliveira Hugo,
Pires Liliana R.,
Fernandez Ramon,
Martins M. Cristina L.,
Simões Sérgio,
Pêgo Ana P.
Publication year - 2010
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.32874
Subject(s) - dorsal root ganglion , transfection , ethylene glycol , materials science , chitosan , peripheral nervous system , peg ratio , biophysics , cell culture , gene delivery , oligonucleotide , microbiology and biotechnology , biology , dna , biochemistry , chemistry , spinal cord , central nervous system , neuroscience , organic chemistry , finance , economics , genetics
A non‐toxic, targeted, simple and efficient system that can specifically transfect peripheral sensorial neurons can pave the way towards the development of new therapeutics for the treatment of peripheral neuropathies. In this study chitosan (CH), a biodegradable polymer, was used as the starting material in the design of a multicomponent vector targeted to the peripheral nervous system (PNS). Polycation‐DNA complexes were optimized using imidazole‐ and thiol‐grafted CH (CHimiSH), in order to increase transfection efficiency and allow the formation of ligand conjugated nanocomplexes, respectively. The 50 kDa non‐toxic fragment from the tetanus toxin (HC), shown to interact specifically with peripheral neurons and undergo retrograde transport, was grafted to the binary complex via a bi‐functional poly(ethylene glycol) (HC‐PEG) reactive for the thiol moieties present in the complex surface. The targeting of the developed nanocomplexes was assessed by means of internalization and transfection studies in the ND7/23 (neuronal) vs. NIH 3T3 (fibroblast) cell lines. Targeted transfection was further confirmed in dorsal root ganglion dissociated primary cultures. A versatile, multi‐component nanoparticle system that successfully targets and transfects neuronal cell lines, as well as dorsal root ganglia (DRG) primary neuron cultures was obtained for the 1.0 (w/w) HC‐PEG/DNA formulation. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.