Targeting Ligand Core

靶向配体核心 癌症纳米技术的一个主要挑战是如何选择性地将功能性纳米颗粒递送到癌细胞。靶向配体核心的总体目标是提供新的靶向配体，可用于将纳米颗粒导向特定的癌细胞类型，用于项目1，2和3。两种强大的组合文库技术将用于产生所需的靶向配体，包括单结构域抗体（SDA）、单结构域抗体模拟物（SDAM）和2 '-F/2'-OMe RNA适体。分别针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，将确保所需的靶向配体将被快速识别并提供给项目。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）SDA和SDAM。我们还将使用细胞-SELEX和常规SELEX的组合来产生可以特异性结合表达EGFR或间皮素的肺癌细胞的2 '-F和2'-OMe RNA适体（里程碑3）。所得的靶向配体将在远离靶结合区的位点处并入诸如Cys或Lys的官能团，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。

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.