Improving Magnetofection of Magnetic Polyethylenimine Nanoparticles into MG-63 Osteoblasts Using a Novel Uniform Magnetic Field

Chaode Cen,Yong Zhang,Cong Luo,Tongchuan He,Tingyu Li,Yang Bi,Xiaolan Yang,Ming Li,Jun Wu,Xin Zhang,Lina Xie

doi:10.1186/s11671-019-2882-5

Abstract

This study aimed to improve the magnetofection of MG-63 osteoblasts by integrating the use of a novel uniform magnetic field with low molecular weight polyethylenimine modified superparamagnetic iron oxide nanoparticles (PEI-SPIO-NPs). The excellent characteristics of PEI-SPIO-NPs such as size, zeta potential, the pDNA binding and protective ability were determined to be suitable for gene delivery. The novel uniform magnetic field enabled polyethylenimine-modified superparamagnetic iron oxide nanoparticles/pDNA complexes (PEI-SPIO-NPs/pDNA complexes) to rapidly and uniformly distribute on the surface of MG-63 cells, averting local transfection and decreasing disruption of the membrane caused by the centralization of positively charged PEI-SPIO-NPs, thereby increasing the effective coverage of magnetic gene carriers during transfection, and improving magnetofection efficiency. This innovative uniform magnetic field can be used to determine the optimal amount between PEI-SPIO-NPs and pDNA, as well as screen for the optimal formulation design of magnetic gene carrier under the homogenous conditions. Most importantly, the novel uniform magnetic field facilitates the transfection of PEI-SPIO-NPs/pDNA into osteoblasts, thereby providing a novel approach for the targeted delivery of therapeutic genes to osteosarcoma tissues as well as a reference for the treatment of other tumors.

Highlights

Osteosarcoma is the most common malignant bone tumor that mainly affects children and adolescents
polyethylenimine hydrochloride (PEI)-SPIO-NPs/plasmid DNA (pDNA) complex can broadly and uniformly touch the targeted cells in a relatively short period of time in the presence of a magnetic field, which may increase the chance of endocytic uptake in unit area of cells, so as to improve the utilization rate of PEI-SPIO-NPs/pDNA complex and enhance the transfection efficiency
The novel magnetic field generator has been developed to induced a uniform magnetic field, in which the PEI-SPIO-NPs/pDNA complexes are rapidly and uniformly distributed on the surface of Human osteoblasts (MG-63) osteoblasts, thereby averting local transfection and decreasing disruption of the membrane caused by centralization of positively charged PEI-SPIO-NPs/pDNA complexes, Fig. 7 MG-63 osteoblasts transfected with PEI-SPIO-NPs/pDNA or polyethylenimine nanoparticles (PEI-NPs)/pDNA under the condition of no magnetic field, non-uniform magnetic field, or uniform magnetic field

Summary

Introduction

Osteosarcoma is the most common malignant bone tumor that mainly affects children and adolescents. Various physical methods such as gene guns [10], ultrasound [11], and electroporation [12] have been efficiently used in improving transfection. To further improve the magnetofection efficiency of non-viral vectors, Fouriki et al adjusted the frequency and amplitude of an oscillating magnetic field to induce a dynamic mechanical stimulatory effect on magnetic nanoparticles, thereby increasing the probability of coming in contact with the target cells [17]. Oral et al further improved transfection efficiency and reduced cytotoxicity of gene carriers by reversely rotating the hexagonal shaft of the magnet to control the speed and direction of the magnetic field [18]. Vainauska et al used a dynamic gradient magnetic field that was generated by rotating a cylindrical permanent magnet for targeting delivery of magnetic gene carriers [19]

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