Magnetic nanoparticles with surface modification enhanced gene delivery of HVJ-E vector

Abstract

To enter the realm of human gene therapy, a novel drug delivery system is required for efficient delivery of small molecules with high safety for clinical usage. We have developed a unique vector "HVJ-E (hemagglutinating virus of Japan-envelope)" that can rapidly transfer plasmid DNA, oligonucleotide, and protein into cells by cell-fusion. In this study, we associated HVJ-E with magnetic nanoparticles, which can potentially enhance its transfection efficiency in the presence of a magnetic force. Magnetic nanoparticles, such as maghemite, with an average size of 29 nm, can be regulated by a magnetic force and basically consist of oxidized Fe which is commonly used as a supplement for the treatment of anemia. A mixture of magnetite particles with protamine sulfate, which gives a cationic surface charge on the maghemite particles, significantly enhanced the transfection efficiency in an in vitro cell culture system based on HVJ-E technology, resulting in a reduction in the required titer of HVJ. Addition of magnetic nanoparticles would enhance the association of HVJ-E with the cell membrane with a magnetic force. However, maghemite particles surface-coated with heparin, but not protamine sulfate, enhanced the transfection efficiency in the analysis of direct injection into the mouse liver in an in vivo model. The size and surface chemistry of magnetic particles could be tailored accordingly to meet specific demands of physical and biological characteristics. Overall, magnetic nanoparticles with different surface modifications can enhance HVJ-E-based gene transfer by modification of the size or charge, which could potentially help to overcome fundamental limitations to gene therapy in vivo.

Nanoparticle delivery of anti-metastatic NM23-H1 gene improves chemotherapy in a mouse tumor model

“…This phenomenon may be due to the fact that the modified iron oxide nanoparticles can change the microenvironment around cells within a short time and escape from the endosome before lysosomal fusion occurs. 35,44,45 Also, transfection of NM23-H1-GFP in normal lung cells was observed but there was no obvious change of normal tissue from the appearance of lung and tissue sections. So, we suggest that overexpressing the NM23-H1 gene in normal cells has no major effect and may help to resist invasive potential of B16 cells.…”

Dendrimer-Modified Magnetic Nanoparticles Enhance Efficiency of Gene Delivery System

“…For example, superparamagnetic iron oxide nanoparticles have been recognized as a promising tool for the site-specific delivery of drugs and diagnostics agents (5)(6)(7). Magnetic nanoparticles (MNP) have been widely explored to have potentials in applications, such as hyperthermia (8), magnetic resonance imaging contrast agent (9), tissue repair (10), immunoassay (11), drug/gene delivery (12), and cell separation (13). However, few reports are closely associated with use of MNPs as gene transfection vector for cancer therapy.…”

Gene therapy progress and prospects: magnetic nanoparticle-based gene delivery

“…The group investigated protamine sulfate (PS)-coated magnetic nanoparticles and found that by associating these particles to HVJ-E, transfection was improved in vitro in BHK21 cells even with a reduction in the amount of HVJ-E and no evidence of toxicity. 8 However, direct injection of the complex into the livers of BALB/c mice showed that the PS-coated particles did not improve transfection levels, whereas the association of heparin-coated maghemite with the HVJ-E vector did. Generally superparamagnetic iron oxide nanoparticles are used for the magnetic component of the complex.…”