Abstract
Supramolecular polymers formed through host–guest complexation have inspired many interesting developments of functional materials for biological and biomedical applications. Here, we report a novel design of a non-viral gene delivery system composed of a cationic star polymer forming supramolecular complexes with the surface oleyl groups of superparamagnetic iron oxide nanoparticles (SPIONs), for magnetically enhanced delivery of DNA into mammalian cells. The cationic star polymer was synthesized by grafting multiple oligoethylenimine (OEI) chains onto an α-cyclodextrin (α-CD) core. The SPIONs were synthesized from iron(III) acetylacetonate and stabilized by hydrophobic oleic acid and oleylamine in hexane, which were characterized in terms of their size, structure, morphology, and magnetic properties. The synthesized magnetic particles were found to be superparamagnetic, making them a suitable ferrofluid for biological applications. In order to change the hydrophobic surface of the SPIONs to a hydrophilic surface with functionalities for plasmid DNA (pDNA) binding and gene delivery, a non-traditional but simple supramolecular surface modification process was used. The α-CD-OEI cationic star polymer was dissolved in water and then mixed with the SPIONs stabilized in hexane. The SPIONs were “pulled” into the water phase through the formation of supramolecular host–guest inclusion complexes between the α-CD unit and the oleyl surface of the SPIONs, while the surface of the SPIONs was changed to OEI cationic polymers. The α-CD-OEI-SPION complex could effectively bind and condense pDNA to form α-CD-OEI-SPION/pDNA polyplex nanoparticles at the size of ca. 200 nm suitable for delivery of genes into cells through endocytosis. The cytotoxicity of the α-CD-OEI-SPION complex was also found to be lower than high-molecular-weight polyethylenimine, which was widely studied previously as a standard non-viral gene vector. When gene transfection was carried out in the presence of an external magnetic field, the α-CD-OEI-SPION/pDNA polyplex nanoparticles greatly increased the gene transfection efficiency by nearly tenfold. Therefore, the study has demonstrated a facile two-in-one method to make the SPIONs water-soluble as well as functionalized for enhanced magnetofection.
Highlights
Gene delivery is the key step of gene therapy, which is the process of introducing foreign genes such as plasmid DNA or short interfering RNA into host cells [1]
Superparamagnetic iron oxide nanoparticles (SPIONs) of 4 nm in size were synthesized with iron (III) acetylacetonate as the precursor according to a method reported (Figure S2) [17]
The oleyl-coated hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized from iron(III) acetylacetonate
Summary
Gene delivery is the key step of gene therapy, which is the process of introducing foreign genes such as plasmid DNA (pDNA) or short interfering RNA (siRNA) into host cells [1]. For cancer gene therapy, pDNA delivery makes host cells produce therapeutic proteins, while siRNA delivery temporarily down-regulates the expression. Genes are delivered into cells via a vector, which serves both as a protection for the gene from degradation as well as a means to overcome cellular barriers during the delivery process. Non-viral vectors often have poor transfection efficiency, due to the slow diffusion process into cells. Improving the transfection efficiency of non-viral vectors has been a great area of interest [1,2,3,4,5,6,7]
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