Abstract
Ethanolamine (EA) or ethylenediamine (ED)-functionalized poly(glycidyl methacrylate) (PGMA), namely PGEA or PGED, has recently been used as effective gene carriers because of their low cytotoxicity and high transfection efficiency. In this study, a series of PGMA-based supramolecular polycations (PGED-Gd@PGEAs) with magnetic resonance imaging (MRI) functions were readily constructed by assembling multiple adamantine-headed star PGEA (Ad-PGEA) units with a versatile PGED-CD-Gd backbone, which possessed numerous flanking β-cyclodextrin species and Gd3+ ions. The properties of different PGED-Gd@PGEA vectors were systematically characterized, including the plasmid DNA condensation ability, cytotoxicity, gene transfection efficiency, cellular uptake and MRI function. Such supramolecular gene vectors had lower toxicity than ‘gold standard’ polyethylenimine (PEI, 25 kDa). Furthermore, PGED-Gd@PGEAs exhibited significantly higher transfection efficiencies than PEI or the constituent units (PGED-CD-Gd and Ad-PGEA). The chelation of Gd3+ ions imparted the PGED-Gd@PGEA vectors with a good MRI ability without obvious adverse effects. The present design of PGMA-based supramolecular polycations with Gd3+ chelation would provide useful information for the development of low-toxicity and high-efficiency multifunctional gene delivery systems. An intricate polymer complex can carry genes to their cellular targets with high efficiency and low toxicity. Gene therapy has the potential to revolutionize the treatment of diseases such as cancer, but non-viral gene delivery systems are needed to ensure patient safety. Fu-Jian Xu from the Beijing University of Chemical Technology and co-workers have taken steps to reach this goal by assembling cationic polymers and gadolinium (Gd) ions into spherical, supramolecular host-guest complexes. These compounds, based on biocompatible poly(glycidyl methacrylate) and cyclodextrin molecules, can be size adjusted to ensure the nanoparticles have the correct dimensions for optimal cellular uptake. The addition of Gd ions turns the multifunctional delivery device into a magnetic resonance imaging probe for in vivo monitoring of nucleic acid transfer. A series of new poly(glycidyl methacrylate)-based supramolecular polycations with Gd3+ chelation were designed for low-toxicity and high-efficiency multifunctional gene delivery systems.
Highlights
Gene therapy holds potential for treating many severe diseases, such as cancer and genetic diseases.[1]
Numerous novel gene delivery systems have been proposed based on functional cationic polymers, such as polyethylenimine (PEI),[4,5,6,7,8,9] poly(2-(dimethylamino) ethyl methacrylate),[4,10] poly(L-lysine),[11] poly(aspartic acid)[12,13] and polyamidoamine.[14]
We found that ethanolamine (EA) or ethylenediamine (ED)-functionalized poly(glycidyl methacrylate) (PGMA), namely PGEA or PGED, could be used as effective gene carriers.[15,16]
Summary
Gene therapy holds potential for treating many severe diseases, such as cancer and genetic diseases.[1]. To further improve the performance of PGMA-based gene carriers, several strategies have been applied such as polysaccharide introduction and target molecule binding.[16,17] Owing to the dynamically unable ability of supramolecular polymers, the application of supramolecular chemistry for gene delivery has been a hot research topic in the biomedical field.[18,19] The construction of supramolecular polycations via host–guest interaction is a popular strategy for high-efficiency gene delivery systems.[20] In particular, cyclodextrins (CDs) and their derivatives have been widely utilized for constructing supramolecular gene delivery systems, mainly because of their superior biocompatibility.[21,22,23] With the host–guest interaction strategy, we successfully prepared one PGEA-based supramolecular delivery system by tying multiple β-cyclodextrin (β-CD)cored star PGEA polymers to an adamantine-modified linear PGEA backbone.[24] Such PGEA supramolecules markedly increased transfection efficiencies. Further improvements in functionality and the development of new preparation strategies for PGMA-based supramolecular vectors would benefit the construction of better gene delivery systems
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 call
