Abstract
Glucose Transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors, which is an important factor in radioresistance of laryngocarcinoma. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngocarcinoma. GLUT-1 siRNA was designed to inhibit the GLUT-1 expression, but the high molecular weight and difficult drug delivery limited the application. Herein, we constructed a glycolipid polymer chitosan oligosaccharide grafted stearic acid (CSSA) to conjugate siRNA via electrostatic interaction. The characteristics of CSSA and CSSA/siRNA were studied, as well as the radiosensitization effect of siRNA on human laryngocarcinoma epithelial (Hep-2) cells. Compared with the traditional commercial vector LipofectamineTM2000 (Lipo), CSSA exhibited lower cytotoxicity, more efficiently cellular uptake. Incubating with CSSA/siRNA, the survival rates of Hep-2 cells were significantly decreased comparing with either the group before transfection or Lipo/siRNA. CSSA is a promising carrier for efficient siRNA delivery and radiosensitization of laryngocarcinoma.
Highlights
Laryngocarcinoma is a common malignant tumor in the head and neck
Early laryngocarcinoma has been actively treated by surgery or radiotherapy, the five-year local recurrence rate is still 5–10%
We developed a chitosan-based glycolipid polymers chitosan oligosaccharide grafted stearic acid (CSSA)
Summary
Laryngocarcinoma is a common malignant tumor in the head and neck. early laryngocarcinoma has been actively treated by surgery or radiotherapy, the five-year local recurrence rate is still 5–10%. There are many factors affecting the radiation effect of tumor, among which the hypoxia and reoxygenation of tumor tissue play an important role. The radiotherapy dosage for the tumor cells with severe hypoxia is 2–3 times higher than for those with sufficient oxygen supply [2,3,4,5]. The existence of hypoxia cells in malignant tumor is one of the important reasons for radioresistance. Tumors grow rapidly with significant energy requirement, and the glycolysis under hypoxia situation consumes more glucose than the glucose oxidation, the glucose metabolic rates of tumor cells are higher than that of normal cells. Compared with normal cells, tumor cells still use glycolysis as the main form of production capacity even under the condition of sufficient oxygen supply, namely “Warburg effect” [6,7]. The rapid growth of malignant tumor depends on a large amount of glucose intake
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