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Multifunctional Nanoparticles in Diagnosis and Therapy of Pancreatic Cancer

多功能纳米粒子在胰腺癌诊断和治疗中的应用

基本信息

批准号：
7286094
负责人：
PARAS N. PRASAD
金额：
$ 64.34万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-29 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7286094
关键词：
Accounting Address Animals Antibodies Antineoplastic Agents Applications Grants Area Arts Biocompatible Biology Biophotonics Buffaloes Cancer Biology Cancer Etiology Cancer Model Cancer Patient Cancer cell line Ceramics Cessation of life Classification Clinical Collaborations Comprehensive Cancer Center Country Development Diagnosis Diagnostic Disease Disease model Distant Drug Delivery Systems Dyes Early Diagnosis Encapsulated Ensure Evaluation Family Funding Gene Delivery Genetic Predisposition to Disease Genomics Goals Grant Human Hybrids Image In Vitro Individual Institutes Institution Intra-abdominal Lasers Lead Lesion Malignant Neoplasms Malignant neoplasm of pancreas Molecular Monitor Nanotechnology Neoplasm Metastasis Nude Mice Oncogenic Outcome Pancreas Pancreatic Adenocarcinoma Pancreatic Ductal Adenocarcinoma Patients Pharmaceutical Preparations Phase Phase II Clinical Trials Positron-Emission Tomography Pre-Clinical Model Principal Investigator Progress Review Group Publishing Quantum Dots Radiation therapy Research Infrastructure Research Personnel Research Priority Risk Role Signal Pathway Silicon Dioxide Sirolimus Small Animal Imaging Resource Programs Solid Specialized Center Staging Surface Therapeutic Time Transgenic Model Transgenic Organisms Translations United States Unresectable Xenograft Model Xenograft procedure anticancer research base cancer cell improved in vivo indium phosphide inhibitor/antagonist molecular/cellular imaging mortality mouse model multidisciplinary nanobiotechnology nanoimaging nanomaterials nanoparticle nanoparticulate novel novel diagnostics optical imaging outcome forecast photonics pre-clinical programs research study small molecule subcutaneous targeted delivery therapeutic target transcriptomics

项目摘要

DESCRIPTION (provided by applicant): Pancreatic ductal adenocarcinoma is the fourth most common cause of cancer-related mortality in the United States, accounting for nearly 31,000 deaths each year. The vast majority of patients present with locally advanced or unresectable disease, and currently available conventional therapeutic approaches have been minimally successful in ameliorating the dismal prognosis of this malignancy. Nanobiotechnology provides unprecedented opportunities for addressing many of the current pitfalls in the diagnosis and therapy of pancreatic cancer. The current proposal represents a multi-institutional platform partnership between groups with extensive expertise in nanomaterial synthesis and delivery, pancreatic cancer biology, and small animal imaging. Multifunctional hybrid ceramic-polymeric nanoparticles, specifically indium phosphide quantum dots (InP Q-DOTS) and organically modified silica (ORMOSIL) nanoparticles have been developed for comprehensive preclinical evaluation in pancreatic cancer models. Specific Aim 1 of this proposal entails the synthesis of long-circulating (PEGylated), surface-functionalized Q-DOTS and dye-doped ORMOSIL nanoparticles incorporating PET probes ("nanoPET"), for improved imaging of early and metastatic pancreatic cancer in vivo. Specific Aim 2 of this proposal entails synthesis of long-circulating, surface-functionalized ORMOSIL nanoparticles encapsulating the small molecule inhibitor rapamycin (nanorapamycin) for systemic drug delivery to pancreatic cancer. A systematic approach is proposed, including an "optimization" phase comprised of in vitro experiments using human pancreatic cancer cell lines and in vivo studies using conventional subcutaneous xenografts; these studies will then lead into an "application" phase utilizing two preclinical models that faithfully recapitulate human pancreatic cancer biology, including the development of intra-abdominal metastases: first, a novel KRAS-driven transgenic mouse model of pancreatic cancer and second, a spontaneously metastasizing orthotopic xenograft model of human pancreatic cancer established in athymic mice. It is anticipated that clinical translation of these "smart" nanomaterials will lead to improved staging of pancreatic cancer at diagnosis, early detection in "at risk" individuals, and more potent therapeutic benefits for patients with advanced disease. The long-term goal of this proposal remains improvement in patient outcome for a malignancy with near-uniform lethality.

描述（由申请人提供）：