Multi-Functional Gene Vetors Constructed Based On Glycidyl Methacrylate

Gene therapy has been investigated for potential applications in curing cancer, the medical treatment of infection, and innate immunodeficiency, as well as cardiovascular diseases.Instead of virus-based vector systems, more efforts have been made to design different cationic polymers as non-viral gene carriers.High-molecular-weight polycations, which can effectively condense pDNA to be a stable polyplex, were intensively investigated as non-viral vectors.However, these non-viral gene carriers also have shortcomings, including cytotoxicity, low transfection efficiency, single-function, etc.As reported in our earlier works, ethanolamine (EA)-functionalized poly(glycidyl methacrylate) (PGMA) vector (denoted as PGEA) could efficiently mediate gene delivery in some cell lines, while exhibiting very low toxicity.In order to facilitates the performance and multi-functionalization of PGEA carriers, several strategies have been applied in our group, such as self-assembling, polysaccharide modification, target molecule binding etc.First, a series of new low-molecular-weight 2,6-bis(1-methylbenzimidazolyl)pyridinyl (BIP)-terminated ethanolamine-functionalized poly(glycidyl methacrylate)s (BIP-PGEAs) were readily fabricated for effective co-delivery of gene and drug. BIP-PGEAs could form well-defined cationic nanoparticles (NPs) in aqueous solution. They could effectively bind pDNA with appropriate particle size and zeta potential. More importantly, BIP-PGEA NPs demonstrated much higher transfection efficiency than linear PGEA (L-PGEA) and traditional’gold-standard’branched polyethylenimine (25 kDa). Moreover, BIP-PGEA NPs also could effectively entrap hydrophobic anticancer drug (such as 10-hydroxy camptothecin (CPT)). The synergistic antitumor effect of BIP-PGEA-CPT NPs was demonstrated by employing a suicide gene therapy system which contains cytosine deaminase and 5-fluorocytosine (ECD/5-FC).And then, a series of PGMA-based supramolecular gene delivery vectors with magnetic resonance imaging (MRI) function were constructed by atom transfer radical polymerization (ATRP), host-guest interaction and Gd3+ chelating, and the properties of PGMA-based gene delivery vectors were systematically characterized.The results showed supramolecular vectors had lower toxicity than polyethylenimine (PEI, 25kDa), the gold standard of gene delivery vectors. Furthermore, the transfection efficiency of supramolecular vectors is significantly higher than both PEI and PGMA-based carriers. The chelation of Gd3+ gave the vectors good ability of MR imaging without obvious adverse effects.