Nanoscale Encasement and Targeted Delivery of Multifunctional Therapeutic Agents

这组研究人员将开发新型多功能治疗和诊断试剂， 纳米级的输送装置。每个项目的中心目标都是设计和评估各种“智能” 纳米级的货箱(纳米桶)，可以靶向癌细胞，与它们结合，然后卸载到 500000多个分子的一种细胞毒性或放射性药剂。合成纳米制造小组 将制造新的单抗生物偶联物，并与临床医生合作测试其疗效 他们现在在细胞培养试验和临床上使用抗体。该方法将结合新的加载 现有抗癌药物(O‘Halloran)的策略与理论方法(Schatz)设计新药 脂质体，用于合成关节脂质体的高级脂质前体技术(麦克唐纳) 聚合物胶束技术的发展--聚合物圆柱体的纳米制造方法 (奥多姆)这些药物中的每一种最初将与临床小组(Singhal， Tallman，Rosen)在白血病和多发性骨髓瘤的细胞培养模型中。具体的代理也将被 在实体肿瘤模型中进行评估。提议的“纳米机器人”运输系统还可以容纳生物制剂， 影响肿瘤和/或其直接微环境的多肽、酶和生长抑制因子。 因此，这些新材料有可能为必须治疗的癌症提供持续治疗。 长期如此。

This team of investigators will develop novel multifunctional therapeutic and diagnostic agents encased in nanoscale delivery devices. The central goal of each project is to engineer and evaluate a variety of "smart" nanoscale cargo bins (nanobins) that can target cancer cells, bind to them and subsequently unload up to more 500000 molecules of a cytotoxic or radiopharmaceutical agents. The synthetic nanofabrication group will make new bioconjugates of monoclonal antibodies and test their efficacy in collaboration with clinicians who use antibodies now in cell culture assay and in the clinic. The approach will combine new loading strategies for established anticancer drugs (O'Halloran) with theoretical approaches (Schatz) to design novel liposomes, advanced lipid precursors technology for the synthesis of articulated liposomes (MacDonald), development of polymer micelle technology (Nguyen), nanofabrication methods for polymer cylinders (Odom). Each of these agents will initially be evaluated in collaboration with the clinical groups (Singhal, Tallman, Rosen) in cell culture models for leukemia and multiple myeloma. Specific agents will also be evaluated in solid tumor models. The proposed 'Nanobin' cargo systems can also house biological agents, peptides, enzymes and growth-inhibiting factors that impact a tumor and/or its immediate microenvironment. These new materials thus have the potential of providing sustained therapy for cancers that must be treated chronically.