Intracellular Host-Guest Activation of Nanoparticle Therapeutics

描述（由申请人提供）：超分子化学为分子系统的组装和驱动提供工具。主客系统关联的可逆性使装配和拆卸具有“锁和钥匙”的特殊性。在我们提出的研究中，我们将开发基于细胞内主客体驱动的纳米颗粒原疗法的新疗法。这种方法为生物活性材料的创造提供了一种新的策略，使当前系统无法实现多种靶向策略。在我们提出的研究中，我们将基于纳米颗粒-葫芦脲（CB）主客体复合物开发新的纳米颗粒原治疗药物。这些复合物在细胞内与CB的竞争性结合物分离，揭开并激活细胞毒性治疗颗粒。这种细胞内驱动过程将使用质谱技术进行量化。然后，我们将使用独特的细胞内驱动过程来实现新的靶向方法，包括双靶向策略，预计对过度表达多个受体的细胞具有高度特异性。

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.