Tumor Therapy/Annihilation Using a Smart NanoPlatform (SNaP)

纳米技术的出现带来了治疗疾病的新方法的希望。 天哪。特别是，纳米平台的多功能性质非常适合治疗复杂的疾病 涉及几个不同的细胞隔间，例如癌症。项目6的总体目标是 开发和测试基于通用纳米平台的可编程或“智能”纳米平台(Snap 核心。纳米平台已经被设计出来，它将基于主客体进行自发自组装 化学相互作用。该组装依赖于聚乙二醇类聚合物的整合 (PEG)-共轭分子客体，其中聚乙二醇聚合物的远端末端可以连接到 “可编程”元素。这种基于主机-来宾的Nano平台提供了几个优于我们 现有平台：与许多强效药物相关的糟糕的药理特性实际上是 在这种方法中利用，预期的副作用较少，设计高度灵活，适应性强 每个纳米平台内的多种治疗、成像、靶向或其他效应器功能，以及 通过宿主和客体的简单共孵育，纳米平台很容易和快速地编程。 将多个目标元素整合到快照中的能力将用于评估是否较低 亲和力/高亲和力靶向模式代表着靶向认知比目前的HIGH有所改善 亲和力/亲和力低的方法。我们假设中到低亲和力、高亲和力依赖于 交互为平台目标提供了更多的机会，特别是在以下情况下 需要对几种不同的“传感器-配体”进行异质识别。最后，我们将测试它的能力 可编程纳米平台，针对促进肿瘤生长和 恶性肿瘤，包括血管和肿瘤成分，使用同基因和转基因疾病模型。 这些调查的重点将是纳米平台在用于消除残留和 原发肿瘤切除后的转移性疾病。快照猎杀残留物的能力 疾病是纳米平台的潜在优势，因为复发和转移的疾病占了 大多数疾病的发病率。这些研究将为新一代Easy 程序化的多功能纳米平台，可用于治疗人类患者的恶性肿瘤。

The advent of nanotechnology holds the promise of new modalities for the treatment of disease in man. In particular, the multifunctional nature of nanoplatforms is well-suited for complex diseases that involve several different cellular compartments, such as cancer. The overall objective of project 6 is to develop and test programmable, or "smart" nanoplatforms (SNaPs) that are based on common nanoplatform cores. Nanoplatforms have been designed which will undergo spontaneous self-assembly, based on hostguest chemical interactions. The assembly is dependent upon integration of polyethyleneglycol polymer (PEG)-conjugated molecular guests, where the distal terminus of the PEG polymer can be conjugated to "programmable" elements. This host-guest based nanoplatform provides several advantages over our existing platforms: the poor pharmacological properties associated with many potent drugs are actually exploited in this approach, with fewer expected side effects, the design is highly flexible, accommodating multiple therapeutic, imaging, targeting or other effector functions within each nanoplatform, and the nanoplatforms are easily and rapidly programmable by-simple coincubation of the host and guest moieties. The capacity to incorporate multiple targeting elements into the SNaPs will be used to evaluate whether low affinity/high avidity modes of targeting represent an improvement in target cognition over current high affinity/low avidity approaches. We hypothesize that moderate-to-low affinity, high-avidity dependent interactions offer increased opportunities for true "recognition" of the platform target, particularly if heterogenous recognition of several different "sensor-ligands" is required. Finally, we will test the capacity of the programmable nanoplatform to target distinct cell populations that contribute to tumor growth and malignancy, including both vascular and tumor elements, using syngeneic and transgenic models of disease. A focus of these investigations will be the efficacy of the nanoplatform, when used to eradicate residual and metastatic disease, after ablation of the primary tumor. The capacity for SNaPs to hunt and kill residual disease is a potential strength of the nanoplatform, as recurring and metastatic disease accounts for the majority of disease morbidity. These studies will lay the groundwork for a new generation of easily programmed, multifunctional nanoplatforms, amenable to the treatment of malignancy in human patients.