Gene therapy and leukemia
As the previous articles explains, part of the problem with generally applying gene therapy in leukemia and other cancers lies with the viral vectors used in gene delivery. Therefore, a lot of research focuses on alternative gene delivery systems which may be more efficient and safer. A lot of attention has recently been paid to the potential of nanoparticles in gene therapy. Leukemia is one of the diseases for which these particles are under consideration.
Just as with viral delivery systems, use of nanoparticles is not without its problems in leukemic cells.
Genetically engineered monocytes loaded with magnetic nanoparticles can be delivered to tumour sites using magnetic fields, however the spherical shape of the nanoparticles reduces their efficacy as delivery systems. It has been shown, however, by use of the reporter dye fluorescein isothiocyanate (FITC), that magnetic carbon nanotubes are efficiently taken up by the human monocytic leukemia cell line THP-1 with no ill effect on cell viability.
Plasmonic nanobubbles (PNBs) are another innovation with potential for transgene delivery and transfection of leukemia cells. PNBs are are formed as a vapour nanobubble around a transiently heated gold nanoparticle upon exposure to a laser pulse. They have allowed mechanical injection of extracellular cDNA plasmids into the cytoplasm of target living cells, including cultured leukemia cells, detectable by the expression of a green fluorescent protein (GFP). PNB generation and lifetime correlated with the green fluorescent protein expression. Optical scattering facilitated cDNA injection at a single cell level. The PNBs have been shown to be selective, efficient and safe and have great potential as gene delivery systems.
Another nanocarrier, carbonate apatite, can lead to highly efficient delivery and release of DNA and transgene expression in some cells but has poor efficiency in human lymphocytes. However, manipulation of the carbonate apatite by electrostatic association of crystals with fibronectin and/or E-cadherin-Fc enhanced transgene delivery to a human T leukemia cell line. Disruption of actin filaments by cell adhesive protein-embedded particles enhanced transgene expression efficiency even further.
Sources
GUL-ULUDAG, H. et al., 2012. Efficient and rapid uptake of magnetic carbon nanotubes into human monocytic cells: implications for cell-based cancer gene therapy. Biotechnology Letters, 34(5), pp. 989-993
KUTSUZAWA, K. et al., 2009. Disrupting actin filaments promotes efficient transfection of a leukemia cell line using cell adhesive protein-embedded carbonate apatite particles. Analytical Biochemistry, 388(1), pp. 164-166
LUKIANOVA-HLEB, E. et al., 2011. Selective gene transfection of individual cells in vitro with plasmonic nanobubbles. Journal Of Controlled Release: Official Journal Of The Controlled Release Society, 152(2), pp. 286-293
As the previous articles explains, part of the problem with generally applying gene therapy in leukemia and other cancers lies with the viral vectors used in gene delivery. Therefore, a lot of research focuses on alternative gene delivery systems which may be more efficient and safer. A lot of attention has recently been paid to the potential of nanoparticles in gene therapy. Leukemia is one of the diseases for which these particles are under consideration.
Just as with viral delivery systems, use of nanoparticles is not without its problems in leukemic cells.
Genetically engineered monocytes loaded with magnetic nanoparticles can be delivered to tumour sites using magnetic fields, however the spherical shape of the nanoparticles reduces their efficacy as delivery systems. It has been shown, however, by use of the reporter dye fluorescein isothiocyanate (FITC), that magnetic carbon nanotubes are efficiently taken up by the human monocytic leukemia cell line THP-1 with no ill effect on cell viability.
Plasmonic nanobubbles (PNBs) are another innovation with potential for transgene delivery and transfection of leukemia cells. PNBs are are formed as a vapour nanobubble around a transiently heated gold nanoparticle upon exposure to a laser pulse. They have allowed mechanical injection of extracellular cDNA plasmids into the cytoplasm of target living cells, including cultured leukemia cells, detectable by the expression of a green fluorescent protein (GFP). PNB generation and lifetime correlated with the green fluorescent protein expression. Optical scattering facilitated cDNA injection at a single cell level. The PNBs have been shown to be selective, efficient and safe and have great potential as gene delivery systems.
Another nanocarrier, carbonate apatite, can lead to highly efficient delivery and release of DNA and transgene expression in some cells but has poor efficiency in human lymphocytes. However, manipulation of the carbonate apatite by electrostatic association of crystals with fibronectin and/or E-cadherin-Fc enhanced transgene delivery to a human T leukemia cell line. Disruption of actin filaments by cell adhesive protein-embedded particles enhanced transgene expression efficiency even further.
Sources
GUL-ULUDAG, H. et al., 2012. Efficient and rapid uptake of magnetic carbon nanotubes into human monocytic cells: implications for cell-based cancer gene therapy. Biotechnology Letters, 34(5), pp. 989-993
KUTSUZAWA, K. et al., 2009. Disrupting actin filaments promotes efficient transfection of a leukemia cell line using cell adhesive protein-embedded carbonate apatite particles. Analytical Biochemistry, 388(1), pp. 164-166
LUKIANOVA-HLEB, E. et al., 2011. Selective gene transfection of individual cells in vitro with plasmonic nanobubbles. Journal Of Controlled Release: Official Journal Of The Controlled Release Society, 152(2), pp. 286-293
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