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

用于胰腺癌成像和治疗的纳米级金属有机框架

• 批准号: 7962388
• 负责人: Wenbin Lin
• 金额: $ 46.18万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-03 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7962388
• 关键词: Address; Adenocarcinoma Cell; Affinity; Arts; Basic Science; Biodistribution; Blood Circulation; Cancer Patient; Cell Line; Cells; Cisplatin; Complement; Complex; Contrast Media; Dextrans; Diagnosis; Diagnostic Imaging; Disease; Doctor of Medicine; Doctor of Philosophy; Drug Formulations; Drug Monitoring; Early Diagnosis; Generations; Genetically Engineered Mouse; Grant; Half-Life; Hybrids; Image; In Vitro; Instruction; Ions; Kinetics; Lead; Ligands; Link; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of pancreas; Membrane Lipids; Metals; Modification; Molecular; Mus; Nanotechnology; Neoplasm Metastasis; Pancreatic Ductal Adenocarcinoma; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Plant Leaves; Platinum; Principal Investigator; Prodrugs; Research; Research Personnel; Scientist; Solid Neoplasm; Staging; Structure; Surface; Surgical Oncologist; System; Technology; Testing; Therapeutic; Therapeutic Index; Therapeutic Studies; Time; Toxic effect; Toxicology; Treatment Efficacy; Xenograft procedure; anti-cancer therapeutic; base; chemotherapeutic agent; dextran; effective therapy; gemcitabine; imaging modality; imaging probe; in vivo; innovation; mouse model; nanomaterials; nanoparticle; nanoscale; novel; oxaliplatin; pancreatic tumorigenesis; particle; programs; subcutaneous; surface coating; tumor; uptake

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.

描述(申请人提供)：胰腺导管腺癌(PDAC)是最致命的疾病之一，5年存活率只有6%，80%的PDAC患者被诊断为晚期不治之症。拟议的癌症纳米技术平台伙伴关系(CNPP)拨款汇集了一支由合成/材料化学家(林文斌博士)、外科肿瘤学家/癌症生物学家(医学博士叶仁英)和药剂学家/生物物理学家(黄叶博士)组成的团队。以满足为早期诊断提供成像探针的关键需求，以及为更有效地治疗PDAC提供有希望的化疗药物的关键需求。这三位拥有互补专业知识的北卡罗来纳大学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(NMOF)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。NMOF代表了一类独特的杂化纳米材料，能够在分子水平上结合金属和有机成分，并以模块化的方式调整它们的结构和组成。建议的NMOF以金属离子或络合物为核磁共振成像载体，以顺铂或/和吉西他滨前药为治疗载体。当连接到适当的细胞靶向分子时，NMOF可以选择性和有效地输送到实体瘤中，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PDAC的新型小鼠模型，包括原位异种移植、KRAS驱动的基因工程小鼠模型(GEMM)和患者来源的PDAC异种移植。这些PDAC小鼠模型为测试NMOF作为PDAC原发肿瘤和转移性肿瘤中成像和化疗药物的有效载体提供了很好的机会。我们相信，拟议的研究将带来新一代杂化纳米材料，用于早期发现和更有效地治疗PDAC，从而为癌症患者提供新的纳米技术管理策略。相关性(见说明)：拟议的研究解决了PDAC早期诊断和更有效治疗的关键需求。新的纳米技术创新预计将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。