Nanoscale Metal-organic Frameworks for Imaging and Therapy of Pancreatic Cancer

描述（由申请人提供）：胰腺导管腺癌（PDAC）是最致命的疾病之一，5年生存率为6%，80%的PDAC患者被诊断为晚期无法治愈。拟议的癌症纳米技术平台合作伙伴关系（CNPP）资助组建了一个由合成/材料化学家（林文斌博士），外科肿瘤学家/癌症生物学家（Jen Jen Yeh，医学博士）和制药科学家/生物物理学家（Leaf Huang，博士）组成的团队，以解决提供早期诊断成像探针的关键需求，以及有希望的化疗药物，以更有效地治疗PDAC。三位具有互补专业知识的北卡罗来纳大学研究人员将利用Lin实验室最近开发的基于纳米尺度金属有机框架（NMOFs）的靶向纳米颗粒技术，开发敏感的诊断成像模式和有效的治疗方法。NMOFs代表了一类独特的杂化纳米材料，具有在分子水平上结合金属和有机成分的能力，并以模块化的方式调整其结构和组成。提议的NMOFs含有金属离子或配合物作为MRI成像货物，顺铂或/和吉西他滨前药作为治疗货物。当与适当的细胞靶向分子连接时，NMOFs可以选择性和有效地递送到实体肿瘤中，从而实现胰腺癌的早期诊断和有效治疗。为了补充这一基础科学发现，Yeh实验室建立了新的PDAC小鼠模型，包括原位异种移植、kras驱动的基因工程小鼠模型（GEMMs）和患者来源的PDAC异种移植。这些PDAC小鼠模型为NMOFs作为PDAC原发性和转移性肿瘤显像和化疗药物的有效递送载体的测试提供了一个很好的机会。我们相信本研究将为PDAC的早期发现和更有效的治疗提供新一代的混合纳米材料，从而为癌症患者提供新的纳米技术管理策略。相关性（见说明书）：拟议的研究解决了PDAC早期诊断和更有效治疗的关键需求。新的纳米技术创新有望在多种肿瘤类型中具有广泛的适用性，并使大量不同类型恶性肿瘤的癌症患者受益。

DESCRIPTION (provided by applicant): Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases with a 5-year survival at a dismal 6% and with 80% of PDAC patients diagnosed at advanced incurable stages. The proposed Cancer Nanotechnology Platform Partnerships (CNPP) grant assembles a team of synthetic/materials chemist (Wenbin Lin, Ph.D.), surgical oncologist/cancer biologist (Jen Jen Yeh, M.D.), and pharmaceutical scientist/biophysicist (Leaf Huang, Ph.D.) to address the critical needs of delivering imaging probes for early diagnosis as well as promising chemotherapeutics for more effective treatment of PDAC. The three established UNC investigators with complementary expertise will take the challenge of developing sensitive diagnostic imaging modalities and effective therapies using targeted nanoparticle technology based on nanoscale metal-organic frameworks (NMOFs) that were recently developed in the Lin lab. NMOFs represent a unique class of hybrid nanomaterials with an ability to combine metal and organic components at a molecular level and to tune their structures and compositions in a modular fashion. The proposed NMOFs contain metal ions or complexes as the MRI imaging cargo and cisplatin or/and Gemcitabine prodrugs as the therapeutic cargoes. When linked to appropriate cell-targeting molecules, the NMOFs can be selectively and efficiently delivered to solid tumors to allow for early diagnosis and effective treatment of pancreatic cancer. To complement this basic science discovery, the Yeh lab has established novel mouse models of PDAC including orthotopic xenografts, the KRAS-driven genetically engineered mouse models (GEMMs), and patient-derived PDAC xenografts. These mouse models of PDAC provide a great opportunity for the testing of NMOFs as an effective delivery vehicle for imaging and chemotherapeutic agents in both primary and metastatic tumors of PDAC. We believe that the proposed research will lead to a new generation of hybrid nanomaterials for early detection and more effective therapy of PDAC, and thus providing new nanotechnology management strategies for cancer patients. RELEVANCE (See instructions): The proposed research addresses the critical needs of early diagnosis and more effective treatment of PDAC. The new nanotechnology innovations are expected to have broad applicability across multiple tumor types and benefit a large number of cancer patients with different types of malignancies.