Tumor Therapy/Annihilation Using a Smart NanoPlatform (SNaP)

使用智能纳米平台 (SNaP) 进行肿瘤治疗/消灭

• 批准号: 7067860
• 负责人: Thomas J Kipps
• 金额: $ 12.97万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7067860
• 关键词: cooperative study; laboratory mouse; nanomedicine; neoplasm /cancer therapy; therapy design /development

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.

纳米技术的出现为治疗癌症的新方法带来了希望， 伙计特别是，纳米平台的多功能性质非常适合于复杂的疾病， 涉及几种不同的细胞区室，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） 丹已经设计了纳米平台，其将基于主客体进行自发自组装， 化学相互作用组装依赖于聚乙二醇聚合物的整合 （PEG）-缀合的分子客体，其中PEG聚合物的远端可以缀合至 “可编程”元素。这种基于主客体的纳米平台提供了几个优于我们的纳米平台的优点。 现有的平台：与许多强效药物相关的不良药理学特性实际上 在这种方法中利用，预期的副作用较少，设计非常灵活，适应性强， 在每个纳米平台内具有多种治疗、成像、靶向或其它效应器功能， 通过简单的主体和客体部分的共温育，纳米平台可以容易且快速地编程。 将利用将多个目标要素纳入战略NaP的能力，评估低 靶向的亲和力/高亲合力模式代表了靶认知相对于当前高亲合力模式的改善。 亲和力/低亲合力接近。我们假设，中到低亲和力，高亲和力依赖 互动为平台目标的真正“识别”提供了更多的机会，特别是如果 需要几种不同的“传感器-配体”的异源识别。最后，我们将测试 可编程纳米平台靶向有助于肿瘤生长的不同细胞群， 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。 这些研究的焦点将是纳米平台在用于根除残留和非残留时的功效。 转移性疾病，在原发性肿瘤消融后。SnaPs猎杀残余生物的能力 疾病是纳米平台的潜在优势，因为复发性和转移性疾病占纳米平台的 大多数疾病的发病率。这些研究将为新一代的容易 程序化的多功能纳米平台，适合于治疗人类患者的恶性肿瘤。