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年生存率低至6%，80%的PDAC患者诊断为晚期不可治愈。拟议中的癌症纳米技术平台伙伴关系（CNPP）资助组建了一个合成/材料化学家团队（林文斌博士），外科肿瘤学家/癌症生物学家（Jen Jen Yeh，医学博士），和药物科学家/生物药理学家（Leaf Huang，Ph.D.）以满足输送用于早期诊断的成像探针以及用于更有效治疗PDAC的有前景的化疗剂的关键需求。这三位具有互补专业知识的资深研究人员将接受挑战，利用基于Lin实验室最近开发的纳米级金属有机框架（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疗法。NMOF代表一类独特的杂化纳米材料，其具有在分子水平上将金属和有机组分联合收割机结合并以模块化方式调节其结构和组成的能力。所提出的匪0 F含有金属离子或络合物作为MRI成像货物和顺铂或/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可以选择性地和有效地递送到实体瘤，以允许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实验室建立了新型PDAC小鼠模型，包括原位异种移植物、KRAS驱动的基因工程小鼠模型（GEMM）和患者来源的PDAC异种移植物。PDAC的这些小鼠模型为测试NMOF作为PDAC的原发性和转移性肿瘤中的成像剂和化疗剂的有效递送载体提供了很好的机会。我们相信，拟议的研究将导致新一代的杂化纳米材料的早期检测和更有效的治疗PDAC，从而为癌症患者提供新的纳米技术管理策略。相关性（请参阅说明）：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，并使大量患有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.