Radiation mediated targeting system for delivering chemotherapeutics to tumors

用于向肿瘤输送化疗药物的放射介导的靶向系统

基本信息

批准号：
8391326
负责人：
DONALD G BUERK
金额：
$ 30万
依托单位：
MEDVAS CONCEPTS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-17 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8391326
关键词：
Adverse effects Animal Disease Models Animal Model Binding Biodistribution Blood Vessels Cancer Patient Capital Cell Adhesion Molecules Cell Surface Proteins Cell surface Cities Combined Modality Therapy Communities Data Development Diagnostic Drug Carriers Drug Delivery Systems E-Selectin Economic Development Effectiveness Endothelial Cells Endothelium Ensure Exposure to Freedom Goals Growth Human Immunoliposome Implant In Vitro Industry Integrins Intellectual Property Ionizing radiation Kinetics Label Legal patent Ligands Liposomes Location Malignant Neoplasms Mammary Neoplasms Mammary gland Mediating Modeling Monoclonal Antibodies Mus Normal tissue morphology Organ Pattern Peripheral Pharmaceutical Preparations Pharmacologic Substance Phase Philadelphia Physiological Preparation Publishing Quaker religion RGD (sequence)Radiation Radiation therapy Rodent Model Safety Science Selectins Small Business Innovation Research Grant Surface System Techniques Therapeutic Therapeutic Uses Tissues Toxic effect Transplantation Tubulin Universities Up-Regulation Work Xenograft Model Xenograft procedure base cancer cell cancer therapy chemotherapeutic agent chemotherapy commercialization cytokine design fluid flow in vivo inorganic phosphate meetings member nanoparticle novel peptide E (adrenal medulla)phase 1 study phase 2 study programs research study shear stress success tissue oxygenation tumor tumor growth

项目摘要

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.

描述（由申请人提供）：MedVas Concepts 将开发的产品是一种与放射治疗联合使用的癌症治疗药物靶向载体。该产品利用电离辐射的特性使药物输送选择性与放射治疗相匹配。超过 50% 的癌症患者接受放射治疗、化疗或两者的结合。虽然现代放射治疗技术可以高度适应肿瘤位置，但联合疗法受到大多数全身化疗策略选择性差的限制。我们最近获得了一种药物靶向系统的专利，该系统使用通过暴露于电离辐射而上调的细胞表面蛋白选择性地将化疗药物递送至肿瘤内皮细胞。我们已经证明，接受放射治疗可以显着上调表面靶标，并且可以使用各种分子来确保核心和外周癌组织都被靶向。我们已经证明，我们的系统可用于控制啮齿动物模型中的肿瘤生长，并且多个靶向配体可提高递送效率。在这一第一阶段提案中，我们打算证明概念验证，即我们产品的双功能形式可以选择性地将血管破坏剂递送至内皮细胞，并更有效、更安全地抑制疾病动物模型中的肿瘤生长。公共健康相关性：该提案将提高放射和化疗联合治疗癌症的有效性和安全性。目前的联合治疗因药物的癌症选择性较差而受到限制。这里正在开发的产品将是第一个药物输送系统，使用聚焦辐射引导化疗药物到达癌细胞，同时使正常组织免受副作用。