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得能够容易地组装和拆卸，再加上“锁和钥匙”的特异性。在我们提出的研究中，我们将开发基于纳米颗粒前疗法的细胞内主客体致动的新疗法。这种方法为生物活性材料的产生提供了一种新的策略，这将使当前系统无法实现多种靶向策略。 在我们提出的研究中，我们将开发新的纳米颗粒前疗法的基础上纳米颗粒-葫芦脲（CB）的主客体复合物。这些复合物在CB的竞争性结合剂的存在下在细胞内解离，暴露并激活细胞毒性颗粒治疗剂。将使用质谱技术定量该细胞内驱动过程。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，包括预计对过表达多种受体的细胞具有高度特异性的双靶向策略。 公共卫生相关性：纳米颗粒治疗剂的超分子致动将为靶向治疗提供新的策略。

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. PUBLIC HEALTH RELEVANCE: Supramolecular actuation of nanoparticle therapeutics will provide new strategies for targeted therapy.