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Oncogenic K-RAS, one of the major histologic subtypes of Non-Small-Cell Lung Cancer (NSCLC) accounts for 25% of the lung cancer related deaths. Hsp90, a ubiquitously expressed molecular chaperone is considered to be a promising target for therapeutic intervention. It is known to interact with several client proteins that are important in the pathogenesis of the cancer. Ganetespib, an Hsp90 inhibitor has been shown to have superior anti-tumor activity in several K-RAS mutant NSCLC cell lines. In addition, lactonic sophorolipids (LSL), a class of chemo-enzymatically modified glycolipids, are known to be promising immunomodulators and have shown to decrease the mortality rate in rat model of sepsis by down-regulating pro-inflammatory cytokines. Recent studies have also demonstrated the anticancer activity of LSL on several cell lines including esophageal, lung and pancreatic cancer cells. HDAC inhibition pathway is to be the best target for antitumor activity of LSL, where the histone deacetylases are inhibited and interferes with the gene expression thereby inducing cytotoxicity and leading to apoptosis. Herein, unique drug cocktail comprising of ganetespib and LSL targeting Hsp90 signaling and inflammatory pathways will be used for NSCLC therapy. Owing to its redox active properties, nanoceria (NC) will be specifically used as the drug delivery platform to supplement the therapeutic potency of the drugs. In this study, LSL and ganetespib carrying nanoceria will be formulated for the targeted treatment of NSCLC.

Detail experimental results including, targeted drug delivery, cytotoxicity, drug release and fluorescence microscopy will be discussed.



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