Radiation mediated targeting system for delivering chemotherapeutics to tumors

描述(由申请人提供)：该产品将由MedVas Concepts开发，是一种用于癌症治疗与放射治疗相结合的药物靶向载体。该产品利用电离辐射的特点，使药物输送的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，或两者兼而有之。虽然现代放射治疗技术对肿瘤的位置高度可调，但联合治疗受到大多数全身化疗策略选择性较差的限制。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中上调的细胞表面蛋白，选择性地将化疗药物输送到肿瘤内皮细胞。我们已经证明，暴露在放射治疗中的表面靶点显著上调，并且各种分子可以用来确保核心和外围癌症组织都是靶向的。我们已经证明，我们的系统可以用来控制啮齿动物模型中的肿瘤生长，并且多个靶向配体可以提高递送效率。在这个第一阶段的提案中，我们打算证明概念证明，我们产品的双功能化形式可以选择性地将血管干扰剂输送到内皮细胞，并在疾病的动物模型中更有效、更安全地抑制肿瘤生长。 与公共卫生相关：这项提议将提高联合放射和化疗治疗癌症的有效性和安全性。目前的联合治疗受到药物对癌症选择性差的限制。这里正在开发的产品将是第一个 一种药物输送系统，利用聚焦的辐射将化疗药物引导到癌细胞，同时使正常组织免受副作用。

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.