Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/120738
Author(s): Santos, J
Moreno, PM
Mansur, A
Leiro, V
Mansur, H
Pêgo, AP
Title: Functionalized chitosan derivatives as nonviral vectors: Physicochemical properties of acylated N,N,N-trimethyl chitosan/oligonucleotide nanopolyplexes
Publisher: The Royal Society of Chemistry
Issue Date: 2015
Abstract: Cationic polymers have recently attracted attention due to their proven potential for nonviral gene delivery. In this study, we report novel biocompatible nanocomplexes produced using chemically functionalized N,N,N-trimethyl chitosan (TMC) with different N-acyl chain lengths (C 5 -C 18 ) associated with single-stranded oligonucleotides. The TMC derivatives were synthesized by covalent coupling reactions of quaternized chitosan with n-pentanoic (C 5 ), n-decanoic (C 10 ), and n-octadecanoic (C 18 ) fatty acids, which were extensively characterized by Fourier transform-infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance ( 1 H NMR). These N-acylated TMC derivatives (TMC n ) were used as cationic polymeric matrices for encapsulating anionic 18-base single-stranded thiophosphorylated oligonucleotides (ssONs), leading to the formation of polyplexes further characterized by zeta potential (ZP), dynamic light scattering (DLS), binding affinity, transfection efficiency and in vitro cytotoxicity assays. The results demonstrated that the length of the grafted hydrophobic N-acyl chain and the relative amino:phosphate groups ratio (N/P ratio) between the TMC derivatives and ssON played crucial roles in determining the physicochemical properties of the obtained nanocomplexes. While none of the tested derivatives showed appreciable cytotoxicity, the type of acyl chain had a remarkable influence on the cell transfection capacity of TMC-ssON nanocomplexes with the derivatives based on stearic acid showing the best performance based on the results of in vitro assays using a model cell line expressing luciferase (HeLa/Luc705).
Subject: Cell Survival/drug effects
Chitosan/chemistry
Chitosan/metabolism
Chitosan/toxicity
Dynamic Light Scattering
Fatty Acids/chemistry
HeLa Cells
Humans
Magnetic Resonance Spectroscopy
Nanoparticles/chemistry
Nanoparticles/toxicity
Oligonucleotides/chemistry
Oligonucleotides/metabolism
Spectroscopy, Fourier Transform Infrared
Transfection
URI: https://hdl.handle.net/10216/120738
Source: Soft Matter, vol. 11(41), p. 8113-8125
Related Information: info:eu-repo/grantAgreement/FCT/5876-PPCDTI/115124/PT
info:eurepo/grantAgreement/FCT/5876-PPCDTI/116372/PT
info:eurepo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F69110%2F2010/PT
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:I3S - Artigo em Revista Científica Internacional

Files in This Item:
File Description SizeFormat 
Functionalizedchitosanderivativesasnonviralvectorsphysicochemical.pdf2.12 MBAdobe PDFThumbnail
View/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.