Project 1: Nanoshells Enabled Tumor Ablation and Immunotherapy

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Abstract Studies have indicated that ablative therapies may augment the host immune system response against tumor antigens by enhancing the local immunogenicity of the ablated tumor as well as distal metastatic sites thereby improving therapy outcomes. The proposed project aims to evaluate the synergy of mechanical HIFU using gas filled silica nanoshells in combination with an immune adjuvant, a TLR7 agonist, which will be conjugated to the surface of silica nanoshells. It is postulated that applying mechanical HIFU to the tumor will condition the tumor tissue environment by exposing tumor antigens without denaturing the proteins and by initiating an inflammatory response. Preliminary studies have shown that the immunostimulatory properties of a TLR7 agonist are enhanced when conjugated to 100nm silica nanoshells. These nanoshell conjugates will be used as an immune adjuvant in order to enhance the antitumor immune response. Combination of HIFU ablative therapy and an immune adjuvant will be investigated in a metastatic colon and breast cancer murine model with the aim to enhance tumor ablation, reduce tumor growth, and to elicit a systemic antitumor immune response. The partnership will be used as a mean to support students underrepresented in science to become young independent scientists. The project will provide many opportunities to promote a learning and collaborative environment for students in research education. This will aid students to develop technical and interpersonal skills which will assist them in fulfilling a successful career.