Investigation of the Role of Glucose Decorated Chitosan and PLGA Nanoparticles as Blocking Agents to Glucose Transporters of Tumor Cells.

Abstract

PurposeGlucose decorated PLGA and chitosan nanoparticles (GPNPs and GCNPs) have been developed to examine the possibility of preventing the facilitated glucose transport to the cells through blocking the glucose transporters (Gluts) overexpressed by tumor cells.MethodsThe MTT assay was used to assess the cytotoxicity towards human colon tumor (HT-29) cells in 72 hrs. Fluorescence microscopy was employed to confirm the attachment of GPNPs to the cells. Moreover, the GPNPs effects on the apoptotic rate of HT-29 cells were analyzed. Finally, the expression levels of GLUT-1 and GLUT-4 by real-time polymerase chain reaction (RT-PCR) were assayed to investigate the response of HT-29 cells to blocking their Gluts by GPNPs.ResultsThe stability studies showed that the synthesized complexes were mostly stable (more than 80%) at various temperatures (4 to 40ºC) and pH (5.4 to 7.4) conditions. Results indicated that the survival rate of the cells was decreased to 43% and 46% after treatment with GCNPs and GPNPs, respectively. Also, the apoptosis assay results showed that the percentage of viable cells reduced to 47% after GPNPs treatment. These observations were justified by the specific interactions between the glucose terminals and the cells Gluts which resulted in blocking the entries of nutrients to the cells. It was revealed that the GLUT-1 mRNA expression after the first 24 h of treatment by GPNPs was upregulated to more than 145%, while the direction was reversed after 72 h (expression less than 45%), which coincided with the cells death. In the first 24 h, the glucose deprivation stimulated the expression of Glut-1 while the apoptotic enzymes expression was dominant at the end of 72 h treatment time.ConclusionFinally, it can be concluded that the glucose-nanoparticle complexes could be considered as promising agents in cancer therapy.