Targeting Ligand Core

靶向配体核心

基本信息

批准号：
8540387
负责人：
Rihe Liu
金额：
$ 7.43万
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：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8540387
关键词：
Adenocarcinoma Cell Affinity Animals Antibodies Binding Biological Markers Bladder Brain Breast CCNE1 gene Cancer Center 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 Generations Head and neck structure Human Investigation Libraries Ligands Lung Lung Adenocarcinoma Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of ovary Malignant neoplasm of pancreas Mesothelioma Messenger RNA Mus Nanotechnology Nature Non-Small-Cell Lung Carcinoma Nucleic Acids 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 functional nanoparticles to cancer cells. The overall thrust of the Targeting 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 targeting 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 nucleic acid-based biomolecules, respectively, will ensure that the desired targeting 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 combination 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 conjugation with various nanoparticles that are used in Projects 1, 2, and 3.

靶向配体核心癌症纳米技术的一大挑战是如何选择性地将功能性纳米颗粒递送至癌细胞。靶向配体核心的总体目标是提供新型靶向配体，可用于将纳米粒子引导至项目 1、2 和 3 的特定癌细胞类型。将使用两种强大的组合库技术来生成所需的靶向配体，包括单域抗体 (SDAs)、单域抗体模拟物 (SDAM) 和 2'-F/2'-OMe RNA 适体。分别对基于蛋白质和基于核酸的生物分子使用两种不同的技术将确保快速鉴定所需的靶向配体并将其提供给项目。具体来说，我们将创建对 EGFR、间皮素和其他有前途的癌症生物标志物具有高亲和力和特异性的单体（里程碑 1）和多聚体（里程碑 2）SDAs 和 SDAMS。我们还将使用cell-SELEX和常规SELEX的组合来生成2'-F和2'-OMe RNA适体，它们可以特异性结合表达EGFR或间皮素的肺癌细胞（里程碑3）。所得的靶向配体将在远离靶标结合区域的位点处掺入诸如 Cys 或 Lys 等官能团，以促进与项目 1、2 和 3 中使用的各种纳米颗粒的位点特异性缀合。