Targeting Hsp90 gene expression by 17-AAG-loaded PLGA/PEG nanoparticles in lung cancer cells
Targeting Hsp90 gene expression by 17-AAG-loaded PLGA/PEG nanoparticles in lung cancer cells
Sona Talaei,1,*Hasan Mellatyar,2
1. Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran 2. Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
Introduction: Hsp90 is overexpressed in cancer cells that are considerably dependent on the function of Hsp90. 17-allylamino-17-demethoxygeldanamycin (17-AAG) inhibits Hsp90 expression and function. 17-AAG has weak water solubility, which is a possible problem for its clinical application. In this study, poly (lactic acid-co-glycolic acid)-poly (ethylene glycol) (PLGA-PEG) nanoparticles are used for improving the stability and solubility of 17-AAG in drug delivery systems.
Methods: Encapsulation of 17-AAG was performed by the double emulsion method, then the amount of loaded drug was calculated. 17-AAG-loaded PLGA-PEG nanoparticles are characterized using H nuclear magnetic resonance (HNMR) and Fourier Transform Infrared (FTIR). For assessing cytotoxicity of PLGA-PEG nanoparticles loaded with 17-AAG on the grown of lung cancer cells, the colorimetric cell viability (MTT) assay was used. Cells were treated with equal concentrations of free 17-AAG and 17-AAG-loaded PLGA-PEG nanoparticles, and Hsp90 gene expression levels in the two groups were compared by real-time PCR.
Results: Regarding the amount of 17-AAG load, IC50 was significantly reduced in cells treated with nanoencapsulated 17-AAG compared to free 17-AAG. This result was confirmed by the decrease of Hsp90 gene expression by real-time PCR.
Conclusion: The results demonstrated that PLGA-PEG-17-AAG complexes are more effective in comparison with free 17-AAG for down-regulating of expression of Hsp89 by increasing uptake by cells. Therefore, PLGA-PEG can be a superior carrier for this kind of hydrophobic agent.