Nanovectors for Characterization and Destruction of Breast Tumor Vasculature

用于表征和破坏乳腺肿瘤脉管系统的纳米载体

基本信息

批准号：
7503965
负责人：
MAURO FERRARI
金额：
$ 39.25万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-28 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7503965
关键词：
3-Dimensional Ablation Adverse effects Affinity Animal Model Applications Grants Aptamer Technology Area Bacteriophages Bioinformatics Biological Biological Markers Biomedical Engineering Biometry Blood Vessels Cancer Biology Cancer cell line Clinical Clinical Treatment Clinical Trials Computer Simulation Computers Cytotoxic agent Development Diagnostic Procedure Doxorubicin Drug Formulations Encapsulated Engineering Ensure Evaluation Flow Cytometry Fractionation Gene Delivery Generations Goals Gold Growth Health Sciences Human In Vitro Italy Lesion Libraries Ligands Liposomes Local Therapy Localized Malignant Neoplasms Malignant neoplasm of pancreas Mammary Neoplasms Mass Spectrum Analysis Medical Medicine Methods Modality Molecular Molecular Biology Molecular Profiling Molecular Weight Monitor Nanomanufacturing Nanotechnology Neoplasm Metastasis Ohio Oligonucleotides Patients Peptides Phage Display Pharmaceutical Preparations Plasma Process Proteins Proteome Proteomics RNA Phages Reporter Research Research Personnel Screening procedure Serum Serum Proteins Signal Transduction Silicon Site Small Interfering RNA Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Staging Structure Technology Testing Texas Therapeutic Therapeutic Agents Time Treatment Efficacy Universities University of Texas M D Anderson Cancer Center Validation Vascular Endothelium angiogenesis aptamer base case control chemical synthesis chemotherapeutic agent combinatorial data mining density design desire experience improved in vivo innovation malignant breast neoplasm mathematical model nanoparticle nanoparticulate nanosized nanovector novel particle phosphorodithioic acid phosphorothioate predictive modeling programs protein expression receptor selective expression success targeted delivery tumor tumor xenograft vascular bed

项目摘要

DESCRIPTION (provided by applicant): The vascular endothelium functions both as a barrier and as a targeting site during development and metastasis of breast tumors. The HYPOTHESIS for studies in our application is that novel nanovectors to capture proteins associated with angiogenic blood vessels for use to selectively target these structures and to deliver therapeutic agents to vascular compartments surrounding human breast tumors provides disruptive technology that will overcome the significant barriers that are currently present in transport of therapeutic agents from the vascular compartment to the site of breast tumors. This BRP R01 proposal brings together an interdisciplinary, multi-institutional team of established investigators from University of Texas Health Sciences Center, UT-MD Anderson Cancer Center, UT-Medical Branch at Galveston, The Ohio State University, and the University Magna Graecia, Catanzaro, Italy who collectively have expertise in all of the necessary areas to achieve the goals of identifying molecular signatures of breast tumors and their associated vasculature to enable targeting and destruction of breast tumors and blood vessels using nanovectors. The areas of expertise include nanovector development and refinement, breast cancer biology, molecular biology, vascular targeting using page display approaches, development of small interfering RNAs in neutral liposomes for tumor targeting, development of novel aptamers for tumor targeting, 3-dimensional mathematical modeling of the vasculature, proteomics using Mass Spectrometry, biostatistics and data mining. To accomplish these goals, the following Specific Aims are proposed: 1). Define known and as yet unidentified proteins using novel nanochips for fractionation and elution of low molecular weight peptides present in serum, and produced by breast tumors and vasculature. 2). Identify molecular signatures associated with angiogenic processes within the vasculature and serum peptidome of the breast tumor microenvironment using phage display libraries and ablate breast tumor vasculature with targeted gold-phage nanoparticle assemblies as signal reporters and drug/gene delivery carriers; and 3). Refine multi-stage nanovectors combined with quantitative computer modeling to selectively target the vasculature associated with breast tumors combined with time-regulated delivery modalities to optimally overcome the biobarriers for effective destruction of breast tumors and their adjacent vasculature.

描述（由申请人提供）：在乳腺肿瘤发育和转移过程中，血管内皮既是屏障和靶向位点的作用。在我们应用中进行研究的假设是，捕获与血管生成血管相关的蛋白质的新型纳米植物，用于选择性地靶向这些结构，并将治疗剂传递到围绕人类乳腺肿瘤的血管箱中的治疗剂提供破坏性技术，从而可以克服从乳房隔离术的治疗剂中目前在治疗剂中出现的重要障碍，这些障碍是从乳房隔离的部位。该BRP R01提案汇集了来自德克萨斯大学卫生科学中心，UT-MD安德森癌症中心，加尔维斯顿的UT-Medial Branch，俄亥俄州立大学，俄亥俄州立大学的UT-MEDICAL分支机构的跨学科，多机构的团队，汇集了一支统一的横向目标，以实现所有统一的目标，以实现所有目标，以实现莫利克的目标，以实现莫利克的统治地位，脉管系统能够使用纳米腔靶向和破坏乳腺肿瘤和血管。专业知识领域包括纳米植物的发展和改进，乳腺癌生物学，分子生物学，使用页面显示方法的血管靶向，用于肿瘤靶向中性脂质体中的小型干扰RNA的开发，用于肿瘤靶向的新型适应性的新型适应症，用于使用血管的三维数学模型的肿瘤靶向，使用质谱和质谱质谱。为了实现这些目标，提出了以下具体目标：1）。使用新型的纳米芯片定义已知并尚未确定的蛋白质，用于血清中存在的低分子量肽的分馏和洗脱，并由乳腺肿瘤和脉管系统产生。 2）。鉴定使用噬菌体显示库和植物的乳腺肿瘤脉管系统的乳腺肿瘤微环境中与血管生成过程和血清肽组内的血管生成过程相关的分子特征，并以靶向金含量的纳米粒子构成为信号记者和药物/基因递送载体；和3）。精炼多阶段的纳米电炉与定量计算机建模相结合，以选择性地靶向与乳腺肿瘤相关的脉管系统，并结合了时间调节的递送方式，以最佳地克服生物载体，以有效破坏乳腺肿瘤及其相邻的脉管系统。