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Document Type

Graduate Research

Creation Date

Spring 4-8-2015

Department

Polymer Chemistry

Abstract

K-RAS is the most common mutated oncogene associated with Non-Small Cell Lung Cancer (NSCLC). So far there are no available targeted therapies for the direct inhibition on K-RAS. The standard course of treatment for patients with advanced NSCLC, often includes combined therapy using therapeutic drugs. However, repeated failure of these therapies due to resistance (MDR), indicated the urgent need for molecularly targeted therapies. Hsp90 has recently become an attractive molecular target for herapeutic intervention of lung cancer. It is a chaperone protein and known to play a major role in the stability and maturation of several key signal transduction proteins, leading to aberrant cell growth causing cancer. Ganetespib, an Hsp 90 inhibitor, has been shown to have superior antitumor activity in several studies and currently, its efficacy for advanced NSCLC treatment is under clinical trials. In this presentation, a new combination therapy will be discussed for the treatment of K-RAS driven NSCLC by using Hsp90 inhibitor, ganetespib and new plantinum complex will be cytotoxic to the cancer cells. Towards this end, folate decorated theranostic iron oxide nanoparticles were formulated to target NSCLC. The drugs and near infra-red dye Oil were encapsulated using unique solvent diffusion method. The formulated multimodal theranostic nanomedicine was used for the targeted treatment of NSCLC, in vitro. The targeted drug delivery and the drug homing were monitored using optical and MR imaging. Results showed that the formulated nanoplatforms are non-toxic (without the drug) and toxic when drugs were carried. Detailed characterizations and in vitro results will be discussed in this presentation.

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