Targeting Ligand Core

靶向配体核心

• 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
• 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

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.

目标配基核心 癌症纳米技术的一个主要挑战是如何选择性地将功能纳米颗粒输送到癌细胞。Targefing配体核心的主要目的是为项目1、2和3提供新的靶向配体，可用于将纳米颗粒导向特定的癌细胞类型。将使用两种强大的组合库技术来产生所需的靶向配体，包括单域抗体(SDA)、单域抗体模拟(SDAM)和2‘-F/2’-OME RNA适配子。将两种不同的技术分别用于基于蛋白质和基于裸子酸的生物分子，将确保迅速确定所需的靶标配体并提供给项目。具体地说，我们将创建单体(里程碑1)和多聚(里程碑2)SDAs和SDAMS，对EGFR、Mesothelin和其他有前景的癌症生物标记物具有高亲和力和特异性。我们还将使用细胞-SELEX和传统SELEX的组合来产生2‘-F和2’-OME RNA适配子，这些适体可以与表达EGFR或Mesothelin的肺癌细胞特异性结合(里程碑3)。得到的靶向配体将在远离靶标结合区的位置(S)引入功能基团，如半胱氨酸或赖氨酸，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结合。