In vitro gene and drug delivery and targeting to human glioma cells by lipoprotein mimics
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Malignant glioma represents a very difficult therapeutic challenge. One new therapeutic strategy is gene therapy, which involves the delivery to and expression of the therapeutic genes in the cancer cells. In this research, a novel artificial lipoprotein delivery system, which consists of nanoemulsion particles and the incorporated lipidized poly-L-lysine, was developed and evaluated. A model plasmid DNA, pSV-ß -Gal, was carried by this system and transfected human glioma cell line SF-767 in vitro. The plasmid DNA was effectively delivered by this system and the reporter gene was expressed. Compared to Lipofectamine . system, this new delivery system demonstrated similar transfection efficiency but a much lower cytotoxicity. Targeted delivery of therapeutics is another new strategy to treat glioma. The cellular uptake of a cholesterol-based anti-tumor compound, BCH, in liposomal formulation by normal neuron cells and glioma cells was compared. It was found that the cellular uptake of BCH by glioma cells was up to 11 times as high as that by normal neuron cells. In the presence of monoclonal anti-LDL receptor antibody in the culture medium, the cellular uptake of BCH in liposomal formulation by the glioma cells was greatly reduced. The effect of serum on the cellular uptake of BCH in liposome formulation by the glioma cells was also investigated by replacing normal serum with lipoprotein deficient serum. LDL could help the cellular uptake of BCH in liposome formulation by the glioma cells. In addition, the effect of divalent calcium ion and temperature on cellular uptake of BCH in liposome formulation was investigated. These results suggested that LDL receptor played an important role in the uptake of BCH in liposome formulation by the glioma cells. The cytotoxicity of another cholesterol-based anticancer drug, methotrexate-cholesterol, on the glioma cells was also evaluated. In addition, the application of biological protein nanostructure in targeted drug delivery was described.