Targeting Ligand Core

靶向配体核心

基本信息

批准号：
7982958
负责人：
Rihe Liu
金额：
$ 8.19万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7982958
关键词：
Acids Adenocarcinoma Cell Affinity Animals Antibodies Binding Biological Markers Bladder Brain Breast CCNE1 gene Cancer Patient Cancer cell line Cell Line Cells Cervix Uteri Chemotherapy-Oncologic Procedure Clinical Colon Complement Core Facility Disseminated Malignant Neoplasm ERBB2 gene Endometrium Engineering Ensure Epidermal Growth Factor Receptor Esophagus Extracellular Domain Head and neck structure Human Investigation Libraries Ligands Lung Lung Adenocarcinoma Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of pancreas Mesothelioma Messenger RNA Mus Nanotechnology Nature Non-Small-Cell Lung Carcinoma Ovarian Ovary Phase Proteins Quality of life RNA Reporting Site Specificity Stomach Surface Technology Toxicity due to chemotherapy aptamer base cancer cell cancer therapy cell type combinatorial functional group immunogenicity improved interest meetings mesothelin nanoparticle neurotensin mimic 2 novel outcome forecast overexpression self assembly standard of care tumor

项目摘要

Targeting Ligand Core One major challenge in cancer nanotechnology is how to selectively deliver funcfional nanoparticles to cancer cells. The overall thrust of the Targefing Ligand Core is to provide novel targeting ligands that can be used to direct nanoparticles to particular cancer cell types for projects 1, 2 and 3. Two powerful combinatorial library technologies will be used to generate the desired targefing ligands, including single domain antibodies (SDAs), single domain antibody mimics (SDAMs), and 2'-F/2'-OMe RNA aptamers. The use of two different technologies for protein-based and nudeic acid-based biomolecules, respectively, will ensure that the desired targefing ligands will be rapidly identified and made available to the Projects. Specifically, we will create monomeric (milestone 1) and multimeric (milestone 2) SDAs and SDAMS with high affinity and specificity for EGFR, mesothelin, and other promising cancer biomarkers. We will also use a combinafion of cell-SELEX and conventional SELEX to generate 2'-F and 2'-OMe RNA aptamers that can specifically bind to EGFR or mesothelin expressing lung cancer cells (milestone 3). The resulting targeting ligands will incorporate functional groups such as Cys or Lys at site(s) away from the target-binding region, to facilitate site-specific conjugafion with various nanoparticles that are used in Projects 1, 2, and 3.

靶向配体核癌症纳米技术中的一个主要挑战是如何选择性地将功能性纳米颗粒传递给癌细胞。 The overall thrust of the Targefing Ligand Core is to provide novel targeting ligands that can be used to direct nanoparticles to particular cancer cell types for projects 1, 2 and 3. Two powerful combinatorial library technologies will be used to generate the desired targefing ligands, including single domain antibodies (SDAs), single domain antibody mimics (SDAMs), and 2'-F/2'-OMe RNA适体。将两种不同的技术用于基于蛋白质的基于蛋白质和裸酸的生物分子，将确保将迅速鉴定出所需的TARGEFING配体并提供给项目。具体而言，我们将创建具有高亲和力和特异性EGFR，间皮林和其他有前途的癌症生物标志物的单体（里程碑1）和多用体（里程碑2）SDA和SDAM。我们还将使用细胞 - 塞莱克斯和常规SELEX的组合来产生2'-F和2'-OME RNA适体，这些适体可以特异性结合到EGFR或表达肺癌细胞的间皮素或间皮素（Milestore 3）。由此产生的靶向配体将结合远离目标结合区域的现场的CYS或LYS等官能团，以促进项目1、2和3中使用的各种纳米颗粒。