Preparation of 17-AAG loaded poly(ε-caprolactone)-poly(ethylene glycol) Nanofibers for Targeting Hsp90 Gene Expressionin T47D Breast Cancer Cells

Introduction:The expression of Hsp90 is increased in tumor cellssuch as breast cancer cells. 17-Allylamino-17-demethoxygeldanamycin (17-AAG) binds to the ATP–binding pocket of Hsp90 and inhibits formation multi-chaperone complex of Hsp90 that leads to degradation of the Hsp90 client proteins through ubiquitin–proteasome pathway.17-AAG has poor water-solubility which is a potential problem for its clinical application. In this study to improve the solubility of 17-AAG in drug delivery systems, we developedimplantable 17-AAG-loaded PCL-PEGnanofibers. Methods:For this purpose, 17-AAG-loaded PCL-PEG nanofibers were successfully fabricated by electrospinning method and characterized using Field Emission Scanning Electron Microscopy (FE-SEM)and Fourier Transform Infrared (FTIR). To assess cytotoxic effects of 17-AAG-loaded PCL-PEG nanofibersand free 17AAG, a colorimetric cell viability (MTT) assays were performed. Cells were treated with equal concentrations of 17-AAG-loaded PCL-PEG nanofiber and free 17-AAG and Hsp90 gene expression levels in the two groups was compared by real-time PCR. Results: MTT assay confirmed that 17-AAG-loaded PCL-PEG nanofiber enhanced 17-AAG cytotoxicity in T47D cells. This finding was associated with decrease of Hsp90 gene expression. Conclusion: The results demonstrated that 17-AAG-loaded PCL-PEG nanofibersare more effective than free 17-AAG in down-regulating Hsp90 expression. Therefore, PCL-PEG nanofiber could be superior carrier for this kind of hydrophobic agents.

کلیدواژه ها:

Breast Cancer ، Hsp90 ، 17-AAG