It is of crucial importance to modify dextran-based polysaccharides in the design of novel biomedical materials. A simple one-step method, involving the reaction of hydroxyl groups of dextran with R-bromoisobutyric acid in the presence of 1,1 0 -carbonyldiimidazole, was first developed to produce bromoisobutyryl-terminated dextran as multifunctional initiators for subsequent atom transfer radical polymerization (ATRP). Well-defined comb-shaped copolymers (DPDs) composed of nonionic hydrophilic dextran backbones and cationic poly((2-dimethyl amino)ethyl methacrylate) (or P(DMAEMA)) side chains were subsequently prepared via ATRP for nonviral gene delivery. The P(DMAEMA) side chains of DPDs can be further partially quaternized to produce the quaternary ammonium DPDs (QDPDs). DPD and QDPDs can condense pDNA into complex nanoparticles of 100 to 150 nm in sizes. QDPDs exhibit stronger ability to complex pDNA, due to increased surface cationic charges. DPDs can exhibit much lower cytotoxicity and better gene transfection yield than high-molecular-weight P(DMAEMA) homopolymers and "gold-standard" polyethylenimine (25 kDa) in HEK293 and L929 cell lines. DPDs also exhibit efficient gene delivery ability in different cancer cell lines, especially in MCF7 cells where the DPD-mediated transfection efficiency is almost 3 times higher than that of the popular Lipfectamine 2000 transfection reagent. This study demonstrated that grafting low-molecular-weight polymer chains from natural dextran backbones via ATRP is an effective means to produce novel polysaccharide-based nanobiomaterials.
The biocleavable star-shaped vectors (CD-SS-PGEAs) consisting of nonionic β-cyclodextrin (β-CD) cores and disulfide-linked low-molecular-weight poly(glycidyl methacrylate) (PGMA) derivative arms with plentiful flanking secondary amine and hydroxyl groups were successfully proposed for highly efficient gene delivery. A simple two-step method was first adopted to introduce reduction-sensitive disulfide-linked initiation sites of atom transfer radical polymerization (ATRP) onto β-CD cores. The disulfide-linked PGMA arms prepared subsequently via ATRP were functionalized via the ring-opening reaction with ethanolamine (EA) to produce the cationic EA-functionalized PGMA (PGEA) arms with plentiful secondary amine and nonionic hydroxyl units. The cationic PGEA arms can be readily cleavable from the β-CD cores under reducible conditions. Such biocleavable star-shaped CD-SS-PGEA vectors possessed the good pDNA condensation ability, low cytotoxicity, and efficient gene delivery ability.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.