Project 1: Nanoshells Enabled Tumor Ablation and Immunotherapy

摘要 研究表明，消融治疗可以增强宿主免疫系统对肿瘤的反应。 通过增强消融肿瘤和远端转移部位的局部免疫原性来识别抗原 改善治疗结果。拟议的项目旨在评估机械HIFU的协同作用，使用 充气二氧化硅纳米壳与免疫佐剂TLR7激动剂结合，将被偶联 到二氧化硅纳米壳的表面。据推测，将机械HIFU应用于肿瘤将使 通过暴露肿瘤抗原而不使蛋白质变性以及通过启动 炎症反应。初步研究表明，TLR7的免疫刺激特性 当激动剂连接到100 nm的二氧化硅纳米壳时，激动剂被增强。这些纳米壳结合物将被用于 作为免疫佐剂，以增强抗肿瘤免疫反应。HIFU消融剂的联合应用 将在转移性结肠癌和乳腺癌小鼠模型中研究治疗和免疫佐剂 目的是加强肿瘤消融，减少肿瘤生长，并诱导系统抗肿瘤免疫 回应。这一伙伴关系将被用作一种手段，以支持在科学领域代表性不足的学生成为 年轻的独立科学家。该项目将提供许多机会来促进学习和 为学生提供研究性教育的协作环境。这将有助于学生发展技术和 帮助他们实现成功职业生涯的人际交往技能。

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.