Targeted Smart Nanoplatforms for Multimode Imaging

纳米技术为人类疾病的新疗法带来了希望。基于纳米颗粒的方法 提供了比目前的临床方法更大的进步的可能性，以适应多种 每个纳米平台内的治疗、成像、靶向或其他效应器功能。在改进的同时 显像剂和药物的药理学特性纳米平台的多功能性质是 因此非常适合诊断和治疗涉及多种生理因素的复杂疾病 隔室，如癌症。项目3的总体目标是描述血管的影响 目标是在肿瘤内积累新的可编程的“智能”纳米平台(SNAP)。目标1 将研究如何将纳米平台靶向肿瘤胎儿整合素受体-表达在 肿瘤和肿瘤血管--导致这些部位聚集。这些研究将集中在 了解亲和力和亲和力对靶内纳米颗粒最终积累的影响 地点。在目标2中，我们将评估纳米平台的靶向，这些平台在一个 “蜂窝状”核心，基于主-客化学相互作用。组装依赖于集成 聚乙二醇型聚合物(聚乙二醇酯)共轭分子客体。聚乙二醇型聚合物的末端 预先结合到“可编程”元素，如靶向或显像剂。目标和目标 照片的稳定性将与传统的纳米颗粒进行对比测试。AIMS 1和AIMS 2都将采用 禽类肿瘤模型及双报告光学成像小鼠背窗的制备 Gd)携带纳米颗粒。目标3.通过以下方式将多个目标元素纳入快照的能力 将使用主机平台和客体锚定部分的简单比率组合来评估 靶向的组合方法--使用靶细胞上两个不同受体的配体-- 提供比单一目标更具体的任何信息。最后，在目标4中，我们将把研究范围从 简单地成像粒子部位的累积，以测试多功能、可成像的纳米粒子是否可以 在疾病的遗传临床前模型中检测新生肿瘤。这些研究将使用光学和磁共振 小鼠皮下肿瘤生长和转移模型及自发性小鼠模型的成像 肿瘤的发展。我们认为，这些研究应该为新一代 易于编程的多功能纳米平台，适用于成像和可能的治疗 人类患者的恶性疾病。这样的粒子代表着朝着发展的重要的第一步 “现场”可编程、个性化、但可批量生产的诊断/治疗产品。

Nanotechnology holds promise for new treatments for disease in man. Nanoparticle-based approaches offer the possibility of significant advances over current clinical methods accommodating multiple therapeutic, imaging, targeting or other effector functions within each nanoplatform. while improving the pharmacological properties of imaging agents and drugs The multifunctional nature of nanoplatforms is therefore well-suited for the diagnosis and treatment of complex diseases involving multiple physiological compartments, such as cancer. The overall objective of project 3 is to characterize the impact of vascular targeting on the accumulation of new programmable "smart" nanoplatforms (SNaPs) within tumors. AIM 1 will examine the characterize how targeting nanoplatforms to oncofetal integrin receptors - expressed on tumors and tumor vasculature - leads to accumulation within these sites. These studies will focus on understanding the impact of affinity and avidity on the ultimate accumulation of nanoparticle within the target site. In AIM 2. we will assess targeting of nanoplatforms which undergo spontaneous self-assembly on a "honeycomb" core, based on host-guest chemical interactions. Assembly is dependent upon integration of polyethyleneglycol polymer (PEG)-conjugated molecular guests. The distal terminus of the PEG polymers are pre-conjugated to "programmable" elements, such as targeting or imaging agents. The targeting and stability of the SNaPs will be tested against conventional nanoparticles. Both AIMS 1 & 2 will employ MRI of avian tumor models and the dorsal window preparation of optically imaged mice with dual reporter (optical & Gd) bearing nanoparticles. AIM 3. The capacity to incorporate multiple targeting elements into the SNaPs by simple ratiometric combination of the host platform and the guest-anchored moieties will be used to evaluate whether combinatorial approaches at targeting - using ligands for two different receptors on the target cell - offers any increase in specificity over singly targeted. Finally, in AIM 4. we will extend the studies from simply imaging accumulation at particle sites to testing whether multifunctional, imagable nanoparticles can detect nascent tumors in genetic preclinical models of disease. The studies will employ Optical and MR imaging of mouse models of subcutaneous tumor growth and metastasis, and spontaneous murine models of tumor development. We believe that these studies should lay the groundwork for a new generation of easily programmed, multifunctional nanoplatforms, amenable to the imaging and possibly treatment of malignancy in human patients. Such particles represent an important first step towards the development of "on site" programmable and personalized, but mass-producible, diagnostic/therapeutic products.