Abstract
BackgroundPolymer surface-modified inorganic nanoparticles (NPs) provide a multifunctional platform for assisting gene delivery. Rational structure design for enhancing colloidal stability and cellular uptake is an important strategy in the development of safe and highly efficient gene vectors.ResultsHeterogeneous Au-coated Fe3O4 (Fe3O4@Au) NPs capped by polyethylene glycol-b-poly1-(3-aminopropyl)-3-(2-methacryloyloxy propylimidazolium bromine) (PEG-b-PAMPImB-Fe3O4@Au) were prepared for DNA loading and magnetofection assays. The Au outer shell of the NPs is an effective platform for maintaining the superparamagnetism of Fe3O4 and for PEG-b-PAMPImB binding via Au–S covalent bonds. By forming an electrostatic complex with DNA at the inner PAMPImB shell, the magnetic nanoplexes offer steric protection from the outer corona PEG, thereby promoting high colloidal stability. Transfection efficiency assays in human esophageal cancer cells (EC109) show that the nanoplexes have high transfection efficiency at a short incubation time in the presence of an external magnetic field, due to increased cellular internalization via magnetic acceleration. Finally, after transfection with the magnetic nanoplexes EC109 cells acquire magnetic properties, thus allowing for selective separation of transfected cells.ConclusionPrecisely engineered architectures based on neutral-cationic block copolymer-conjugated heterogeneous NPs provide a valuable strategy for improving the applicability and efficacy of synthesized vectors.
Highlights
Polymer surface-modified inorganic nanoparticles (NPs) provide a multifunctional platform for assisting gene delivery
We converted the dithioester of PEG-b-PAMPImB [previously synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization] into a thiol end-group with hydrazine, and obtained PEG-b-PAMPImB-Fe3O4@Au NPs via a strong binding affinity between gold and thiol ending
The clear covered polymer layers observed on the surface of Fe3O4@Au NPs further confirmed that PEGb-PAMPImB attached onto Fe3O4@Au NPs, as these images are clearly different from Transmission electron microscopy (TEM) images of F e3O4 (Additional file 1: Figure S1a) and Fe3O4@Au (Additional file 1: Figure S1b)
Summary
Polymer surface-modified inorganic nanoparticles (NPs) provide a multifunctional platform for assisting gene delivery. The exposed positive surface of these vectors causes undesired aggregation and extensive vector accumulation in the physiological media [18, 19], resulting in impaired intracellular uptake and unsuitability for in vivo applications [20] To overcome these limitations, block copolymers have been introduced which enhance the colloidal stability of Au NP-based vectors by means of a novel three layer micelle-like structure [21]. Our group studied a process of DNA loading and the influence of PEG-b-PAMPImB-capped Au NPs on colloid stability during delivery [24] These vectors exhibited a mono-disperse state to translocate across the cell membrane and partly entered the nucleus, inducing high and efficient gene expression. The neutral outer corona significantly promoted high colloidal stability, it had a negative effect on cellular uptake due to the reduced interaction between vector and cell membrane, called “PEG dilemma” [25, 26]
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