Targeting HSP90 gene expressionby 17-DMAG loaded poly(ε-caprolactone)-poly(ethylene glycol) electrospunnanofibrous scaffolds in T47D breast cancer cells

Introduction: Up-regulation of HSP90 gene takes place in breast cancer cells. Therefore, targeting the HSP90 in breast cancer may be promising step in breast cancer therapy. The present study aimed to evaluate the efficiency of implantable 17-dimethylaminoethylamino-17-demethoxy geldanamycin (17-DMAG)-loaded poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG) nanofibers to increase the anti-cancer effects via inhibition of HSP90 expression. Methods:For this purpose, 17-DMAG-loaded PCL-PEG nanofibers were successfully fabricated via electrospinning technique and characterized using Field Emission Scanning Electron Microscopy (FE-SEM) and Fourier Transform Infrared (FTIR).Colorimetric MTT metabolic activity assay was used to determine the drug cytotoxicity. Also, the expression levels of HSP90 gene in the T47D cells seeded on the scaffolds were assessed using real-time RT-PCR.Results: Taking into account drug load, IC50 was significantly decreased in 17-DMAG-loaded PCL-PEG nanofibers in comparison with free 17-DMAG. This finding was associated with decrease of HSP90 gene expression. Conclusions:17-DMAG-loaded PCL-PEG nanofiber can be more effective than free 17-DMAG in down-regulating of HSP90 expression, at the same time exerting more potent cytotoxic effects. Therefore, PCL-PEG could be a superior carrier for this type of hydrophobic agent.

Keywords:

Breast Cancer , HSP90 , 17-DMAG , Nanofiber