Components Simulation of Viral Envelope via Amino Acids Modified Chitosans for Efficient Nucleic Acids Delivery: in vitro and in vivo Study
writer：Jing Chang, Xianghui Xu, Yeting Jian, Gang Wang, Bin He*, Zhongwei Gu*
keywords：Amino Acids Modified Chitosans
source：期刊
specific source：Adv. Funct. Mater. 2013, DOI: 10.1002/adfm.201202503
Issue time：2013年
Novel nonviral gene vectors of alkaline amino acids such as arginine- (Arg), histidine- (His), and lysine- (Lys) modifi ed chitosans (AAA-CSs) are developed to simulate the components of viral envelopes to enhance transfection effi ciency. The structures of the modifi ed 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 unmodifi ed 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-modifi ed chitosan could signifi-cantly enhance gene-transfection effi ciency both in vitro and in vivo.