Targeted Smart Nanoplatforms for Multimode Imaging

用于多模式成像的靶向智能纳米平台

• 批准号: 7490288
• 负责人: Dwayne G Stupack
• 金额: $ 13.35万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7490288
• 关键词: Address; Advanced Development; Affinity; Avidity; Binding; Biological; Birds; Blood Circulation; Blood Vessels; Cancer Patient; Cells; Cessation of life; Chemicals; Chemistry; Class; Clinical; Complex; Cyclodextrins; Detection; Development; Diagnosis; Diagnostic; Disease; Distal; Dorsal; Drug Kinetics; Drug usage; Elements; Generations; Genetic; Genetic Models for Cancer; Homing; Human; Image; Imagery; In Situ; In Vitro; Integrins; Kinetics; Ligands; Magnetic Resonance Imaging; Malignant Neoplasms; Mediating; Methods; Modality; Modeling; Molecular; Mus; Nanotechnology; Nature; Neoplasm Metastasis; Operative Surgical Procedures; Optical reporter; Optics; Patients; Personal Satisfaction; Pharmaceutical Preparations; Physiological; Pliability; Polymers; Population; Pre-Clinical Model; Predictive Value; Preparation; Primary Neoplasm; Property; Protocols documentation; Relative (related person); Reporter; Residual Tumors; Residual state; Role; Running; Site; Specificity; Surface; System; Testing; Therapeutic; Therapeutic Agents; Titrations; Work; base; chemotherapy; combinatorial; design; improved; in vivo; interest; man; mouse model; nanoparticle; new technology; novel; particle; programs; receptor; self assembly; subcutaneous; targeted delivery; tumor; tumor growth; vector

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.

纳米技术对人类疾病的新疗法有望。基于纳米颗粒的方法 提供比当前临床方法的重大进步的可能性 每个纳米板中的治疗，成像，靶向或其他效应子功能。同时改善 成像剂和药物的药理特性纳米板的多功能性质是 因此非常适合诊断和治疗涉及多种生理的复杂疾病 车厢，例如癌症。项目3的总体目标是表征血管的影响 针对肿瘤中新的可编程“智能”纳米板（快照）的积累。目标1 将检查靶向纳米植物对oncofetal整联蛋白受体的特征 - 在 肿瘤和肿瘤脉管系统 - 导致在这些部位积累。这些研究将重点 了解亲和力和亲和力对纳米颗粒在目标中的最终积累的影响 地点。在AIM 2中。我们将评估纳米植物的靶向，这些纳米植物会自发地自组装 “蜂窝”核心，基于宿主 - 环化学相互作用。组装取决于集成 聚乙二醇聚合物（PEG）偶联的分子来宾。 PEG聚合物的远端末端 预先将“可编程”元素（例如靶向或成像剂）进行预轭。目标和 快照的稳定性将针对常规纳米颗粒进行测试。两个目标1和2将使用 用双报告者（光学＆ gd）带有纳米颗粒。目标3。将多个靶向元素纳入快照的能力 主机平台和客座锚定部分的简单比率组合将用于评估 组合方法是否在靶向方面 - 使用配体用于目标细胞上的两个不同受体 - 与单一目标相比，特异性的提高。最后，在AIM 4中。我们将扩展研究 简单地将粒子位点的积累成像以测试多功能，可成像的纳米颗粒是否可以 检测疾病遗传临床前模型中的肿瘤。研究将采用光学和MR 皮下肿瘤生长和转移和自发鼠模型的小鼠模型的成像 肿瘤发育。我们认为这些研究应该为新一代的基础奠定基础 易于编程的多功能纳米板形，可以适应成像，并可能处理 人类患者的恶性肿瘤。这样的粒子代表着发展的重要第一步 “在现场”可编程和个性化但可实现的诊断/治疗产品。