Targeting HSP90 gene expression by 17-DMAG loaded poly(ε-caprolactone)-poly(ethylene glycol) electrospun nanofibrous scaffolds in A549 lung cancer cells

Abstract

Introduction: Up-regulation of HSP90 gene takes place in lung cancer cells. Therefore, targeting the HSP90 in lung cancer may be promising step in lung 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). The release profile of drug from the drug-loading nanofibers was studied by incubating nanofiber in the release media. Colorimetric MTT metabolic activity assay was used to determine the drug cytotoxicity. Also, the expression levels of HSP90 gene in the A549 cells seeded on the scaffolds were assessed using real-time RT-PCR. Results: Microscopic studies indicated the loading of 17-DMAG into the PCL/PEG nanofiber, successfully. 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.