Abstract
The present study investigated the synthesis of biotinylated chitosan (Bio-CS) from chitosan using a nanomaterial skeleton with biotin and the successful targeting of the formulation in liver cancer cells. Bio-CS was validated by fourier transformed infrared spectroscopy and hydrogen-1 nuclear magnetic resonance spectroscopy. Bio-CS and plasmid DNA were used to construct Bio-CS/plasmid DNA nanoparticles according to the optimal molar ratio of 1:1 and the optimal pH-value of 5.5. Under these conditions, the parameters mean particle size, potential, encapsulation rate and drug loading, were 82.9 nm, +21.8 mV, 85.7% and 35.4%, respectively. Bio-CS exhibited an apparent liver cancer targeting effect in vitro and in vivo, as demonstrated by confocal laser scanning, green fluorescent protein transfection, and in vivo imaging assays. In addition, the Bio-CS/plasmid DNA nanoparticles significantly increased the survival period of the orthotropic liver cancer mouse model compared with the plasmid DNA, with no apparent side effects on the cells. Bio-CS nanomaterials stimulated an immune response in hepatoma cells via increased expression of GM-CSF, IL-21 and Rae-1 markers. The data suggest that Bio-CS increased the inhibition of liver cancer cell proliferation in vitro and the activation of the cellular immunity in vivo.
Highlights
Liver cancer can be therapeutically targeted by enhanced immune surveillance, inhibition of immune escape, activation of the body’s innate immunity and the elevated expression of specific liver cancer markers that can be recognized by the immune system
The present study investigated the synthesis of biotinylated chitosan (Bio-CS) from chitosan using a nanomaterial skeleton with biotin and the successful targeting of the formulation in liver cancer cells
Nanoparticles demonstrate certain advantages for drug delivery and tissue targeting [16, 17]: (1) They can be effectively loaded with antitumor drugs, (2) they exhibit the target group on the particle surface and (3) they contain considerably small size that is estimated in the nanometer range
Summary
Liver cancer can be therapeutically targeted by enhanced immune surveillance, inhibition of immune escape, activation of the body’s innate immunity and the elevated expression of specific liver cancer markers that can be recognized by the immune system. Immune escape can be avoided by the following processes: Host immunity can be stimulated, notably in the context of anti-tumor cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, whereas the expression of antibodies and/or ligands that are recognized by host immunity in cancer cells may be increased [2] An example of the latter process includes the natural killer group 2D (NKG2D). Previous studies conducted by our group, demonstrated the construction of pGM-CSF-GFP-IRES-Rae-1-IL-21 as an “immune escape system” The latter process can improve the activity of NK and CTL cells, reduce the percentage of regulatory T cells, increase the expression of NKG2D ligand Rae-1 in hepatocellular carcinoma cells and promote the recognition of hepatocellular carcinoma cells by CTL and NK cells in order to enhance immune surveillance and inhibit immune escape [7]. The safe and systematic transport of this system to the liver cancer cells warrants further investigation
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