Year-end Sale % OFF 
Abstract
Lack of capacity to cross the nucleus membrane seems to be one of the main reasons for the lower transfection efficiency of gene vectors observed in vivo study than in vitro. To solve this problem, a new non-viral gene vector was designed. First, a degradable polyethylenimine (PEI) derivate was synthesized by crosslinking low-molecular-weight (LMW) PEI with N-octyl-N-quaternary chitosan (OTMCS), and then adopting a designed trifunctional peptide (RGDC-TAT-NLS) with good tumor targeting, cell uptake and nucleus transport capabilities to modify OTMCS-PEI. The new gene vector was termed as OTMCS-PEI-R18 and characterized in terms of its chemical structure and biophysical parameters. Gene transfection efficiency and nucleus transport mechanism of this vector were also evaluated. The polymer showed controlled degradation and remarkable buffer capabilities with the particle size around 100–300 nm and the zeta potential ranged from 5 mV to 40 mV. Agraose gel electrophoresis showed that OTMCS-PEI-R18 could effectively condensed plasmid DNA at a ratio of 1.0. Besides, the polymer was stable in the presence of sodium heparin and could resist digestion by DNase I at a concentration of 63U DNase I/DNA. OTMCS-PEI-R18 also showed much lower cytotoxicity and better transfection rates compared to polymers OTMCS-PEI-R13, OTMCS-PEI and PEI 25 KDa in vitro and in vivo. Furthermore, OTMCS-PEI-R18/DNA complexes could accumulate in the nucleus well soon and not rely on mitosis absolutely due to the newly incorporated ligand peptide NLS with the specific nuclear delivery pathway indicating that the gene delivery system OTMCS-PEI-R18 could reinforce gene transfection efficiency in vivo.
Highlights
Cancer remains a global health problem and a major cause of death worldwide
We developed a new non-viral gene vector OTMCS-PEI-R18 by cross-linking LMW PEI with OTMCS and further coupled with a trifunctional peptide R18 for specific tumor targeting, cellular and nucleus transport
Through characterization of its chemical structure and biophysical parameters, the polymer OTMCS-PEI-R18-l could condense plasmid DNA to nanoparticle at the weight ratio about 0.8
Summary
Cancer remains a global health problem and a major cause of death worldwide. Statistical analysis published by the International Agency for Research on Cancer from WHO reveals that if the estimated trends continue, the incidence of all cancer cases will raise from 12.7 millionPLOS ONE | DOI:10.1371/journal.pone.0166673 December 9, 2016A Biodegradable Gene Vector for In Vivo Gene Transfection had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
