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Document Type

Undergraduate Research

Creation Date

Spring 4-8-2015




Mutations in K-RAS are prevalent in 25% of Non-Small Cell Lung Cancer (NSCLC) and so far are considered to be undruggable. K-RAS is known to be the primary monogenic driver in NSCLC and more common in smokers. For the enhanced effectiveness of K-RAS inhibition, Hsp90 inhibitor has been used. The Hsp90, a molecular chaperone known to affect multiple signaling cascades, facilitates aberrant cancer cell survival by protecting mutated on coproteins from targeted degradation. In this presentation, a new combination therapy will be discussed for the treatment of K-RAS driven NSCLC to using Hsp9- inhibitor, Ganestespib and therapeutic drug taxol. Towards this end, new biocompatible hyperbranched polyester was developed, capable of formulating cancer targeting theranostic nanoplatform. The projected aliphatic dendritic polyester is spherical in shape, indicating the presence of enough polymeric cavities for the effective encapsulations of therapeutic drugs, Hsp90 inhibitor and other cargos. The formulated nanomedicine was labelled with near infra-red optical dye (Oil) for optical imaging, whereas encapsulation of BiDOTA complex added X-ray imaging modality to monitor drugs (Ganetesib and taxol) homing. Nanotechnology based modern techniques were used to facilitate such molecular encapsulation processes. The surface of the polymeric nanoparticles was decorated with small molecule folic acid using “click” chemistry. Results showed that the formulated nanoplatform is non-toxic (without the drug) and able to cross the A549 cell membrane by the folate receptor-mediated internalizations (Figure). Further results with the combination therapy of NSCLC will be discussed in this presentation.


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