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Components Simulation of Viral Envelope via Amino Acid Modified Chitosans for Efficient Nucleic Acid Delivery: In Vitro and In Vivo Study
Author(s) -
Chang Jing,
Xu Xianghui,
Li Haiping,
Jian Yeting,
Wang Gang,
He Bin,
Gu Zhongwei
Publication year - 2013
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201202503
Subject(s) - transfection , zeta potential , agarose gel electrophoresis , gene delivery , chitosan , in vivo , mtt assay , biophysics , in vitro , materials science , nucleic acid , histidine , amino acid , biochemistry , chemistry , biology , nanoparticle , dna , nanotechnology , gene , microbiology and biotechnology
Novel nonviral gene vectors of alkaline amino acids such as arginine‐ (Arg), histidine‐ (His), and lysine‐ (Lys) modified chitosans (AAA‐CSs) are developed to simulate the components of viral envelopes to enhance transfection efficiency. The structures of the modified chitosans are characterized using 1 H NMR spectroscopy. Acid‐base titration results indicate that the modified chitosans exhibit strong buffering capacity. The morphology of the AAA‐CSs/pDNA complexes is observed by use of transmission electron microscopy and atomic force microscopy. The complexes are spherical nanoparticles with a mean size around 100 nm. Zeta potential tests reveal that the complexes are positively charged and their zeta potentials vary from +0.1 to +19.5 mV. The MTT assay and agarose gel electrophoresis demonstrate that the AAA‐CSs are non‐cytotoxic and have excellent DNA condensation and protection abilities. Cellular uptake investigation of the AAA‐CSs/pDNA complexes demonstrates that Arg‐CS and His‐CS have better cellular internalization property than the unmodified chitosan. The in vitro gene transfection is evaluated in HEK293 and NIH3T3 cell lines and in vivo transfection is carried out in tibialis anterior muscles. The results reveal that the arginine‐modified chitosan could significantly enhance gene‐transfection efficiency both in vitro and in vivo.