Grant: Project Grant

Research challenge Radiotherapy (RT) is one of the main modalities of cancer treatment and more than half of cancer patients can benefit from RT in the management of their disease. Currently, we are at the limit of RT dose given to patients, creating a clear need for novel methods to enhance current RT dose. Our solution If we can enhance the RT dose given to the tumor locally, it will have a tremendous potential to maximize the effect of dose given to the tumor while minimizing normal tissue toxicity. We are proposing to add a unique combination of two radiation dose enhancers such as gold nanoparticles (GNPs) and docetaxel (DTX). GNPs can interact with photons and produce cell damaging species causing more cell death while DTX can put cells in state that they are most sensitive to radiation. GNPs are biocompatible (based on early phase clinical trials) and DTX is clinically approved. Therefore, combination of these two radiation dose enhancers is expected to generate a more desirable outcome with RT. Research objectives The aims for the proposal are two-fold: 1) Determining the efficacy of the proposed DTX/GNPs/RT using three-dimensional tissue (3D) models in vitro. 2) Determining the efficacy of the proposed DTX/GNPs/RT in vivo. Research methodology GNPs of diameter 5, 10, and 50 nm will be functionalized with polyethylene glycol (PEG) and a peptide that can target tumor cells. We will compare two modalities for delivering DTX: 1) free drug as used in the clinic, and 2) use of a lipid NP system as its carrier (LNP-delivery). We chose prostate cancer model since DTX with RT has been tested in prostate cancer patients and higher survival rates have been reported. Significance Our proposed approach of adding two radiosensitizers (with complementary behavior) to current RT protocol will facilitate the necessary boost to significantly enhance the curative RT dose to further improve the survival without any additional normal tissue toxicity.