Intracellular Host-Guest Activation of Nanoparticle Therapeutics

描述(申请人提供)：超分子化学为分子系统的组装和驱动提供了工具。主-客系统关联的可逆性使组装和拆卸变得容易，并具有“锁和钥匙”的专用性。在我们提出的研究中，我们将开发基于纳米颗粒前驱剂细胞内主客体驱动的新疗法。这种方法为创造生物活性材料提供了一种新的战略，这将使现有系统无法实现的多种靶向战略成为可能。在我们提出的研究中，我们将开发基于纳米颗粒-南瓜脲(CB)主客体复合体的新的纳米颗粒治疗药物。在CB竞争性结合剂存在的情况下，这些复合体在细胞内解离，揭开并激活细胞毒颗粒治疗。这种细胞内的激活过程将使用质谱学技术进行量化。然后，我们将使用独特的细胞内激活过程来实现新的靶向方法，包括有望对过度表达多种受体的细胞高度特异的双靶向策略。

DESCRIPTION (provided by applicant): Supramolecular chemistry provides tools for the assembly and actuation of molecular systems. The reversibility of association of host-guest systems enables facile assembly and disassembly coupled with 'lock and key' specificity. In our proposed research we will develop new therapeutics based on intracellular host-guest actuation of nanoparticle protherapeutics. This approach provides a new strategy for the creation of bioactive materials that will enable multiple targeting strategies inaccessible with current systems. In our proposed research, we will develop new nanoparticle protherapeutics based on nanoparticle-cucurbituril (CB) host-guest complexes. These complexes dissociate inside the cell in the presence of competitive binders for CB, unmasking and activating the cytotoxic particle therapeutic. This intracellular actuation process will be quantified using mass spectrometric techniques. We will then use the unique intracellular actuation process to enable new targeting approaches, including dual-targeting strategies that are expected to be highly specific to cells overexpressing multiple receptors.