Radiation mediated targeting system for delivering chemotherapeutics to tumors

描述（由申请人提供）：MedVas Concepts将开发的产品是一种用于癌症治疗与放射治疗联合使用的药物靶向载体。该产品利用电离辐射的特性使药物递送选择性与放射治疗的选择性相匹配。超过50%的癌症患者接受放射治疗或化疗，或两者结合。虽然现代放射治疗技术对肿瘤位置具有高度可调性，但大多数全身化疗策略的选择性差限制了联合治疗。我们最近申请了一项药物靶向系统的专利，该系统利用暴露于电离辐射下上调的细胞表面蛋白，选择性地向肿瘤内皮细胞输送化疗药物。我们已经证明，暴露于放射治疗会显著上调表面靶标，并且可以使用各种分子来确保核心和外周癌症组织都是靶向的。我们已经证明我们的系统可以用于控制啮齿动物模型中的肿瘤生长，并且多个靶向配体提高了递送效率。在这个i期提案中，我们打算证明我们产品的双功能化形式可以选择性地向内皮细胞提供血管破坏剂，并且在动物疾病模型中更有效和安全地抑制肿瘤生长。

DESCRIPTION (provided by applicant): The product that will be developed by MedVas Concepts is a drug targeting vehicle for cancer therapeutics used in combination with radiation therapy. The product uses a feature of ionizing radiation to match drug delivery selectivity with that of the radiation treatment. More than 50% of cancer patients receive radiation therapy, or chemotherapy, or a combination of both. While modern radiation therapy techniques are highly tunable to tumor locations, combination therapies are limited by the poor selectivity of most systemic chemotherapy strategies. We have recently patented a drug targeting system that selectively delivers chemotherapeutics to tumor endothelial cells using cell surface proteins that are upregulated by exposure to ionizing radiation. We have demonstrated that surface targets are significantly upregulated by exposure to radiation therapy, and that various molecules can be used to ensure that both core and peripheral cancer tissues are targeted. We have demonstrated that our system can be used to control tumor growth in a rodent model, and that multiple targeting ligands increase delivery efficiency. In this Phase 1 proposal, we intend to demonstrate proof-of-concept that a bifunctionalized format of our product can selectively deliver a vascular disrupting agent to endothelial cells, and more effectively and safely inhibit tumor growth in an animal model of disease. PUBLIC HEALTH RELEVANCE: This proposal will increase the effectiveness and safety of combined radiation and chemotherapies for cancer treatment. Current combined treatments are limited by the poor cancer-selectivity of drugs. The product being developed here will be the first drug delivery system that uses focused radiation to guide chemotherapeutic agents to cancer cells, while sparing normal tissues from side effects.