Multifunctional and tunable lipid-nanoparticle assemblies

多功能且可调节的脂质纳米颗粒组件

• 批准号: 0931875
• 负责人: Geoffrey Bothun
• 金额: $ 30万
• 依托单位: University of Rhode Island
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0931875&HistoricalAwards=false
• 关键词: Multifunctional; tunable; lipid; nanoparticle; assemblies

Multifunctional nano scale therapeutics represents a transformative new frontier in disease treatment. Liposomes provide a versatile and dynamic platform for encapsulating functional inorganic nanoparticles with different surface chemistries to achieve multiple therapeutic objectives. This project employs original approaches to selectively decorate engineered liposomes with inorganic nanoparticles, and examine how nanoparticle size, charge and hydrophobicity affect liposome structure and function. Such composite assemblies will play an important role in therapeutic applications where spatially as well as temporally targeted delivery is required. Surface functionalized superparamagnetic iron oxide (SPIO) will be used as model nanoparticles, as they have been successfully employed as MRI contrast agents and for in vivo hyperthermia, where heating is achieved using external magnetic fields operating at radio frequencies. Programmed RF stimulation of the magnetoliposomes will provide a simple yet robust way to control liposome structure and stability. Through Aim 1, electrostatically and hydrophobically assembled decorated magnetoliposomes will be formed and their structure, morphology, and colloidal stability characterized. In Aim 2, the effect of selective decoration, SPIO nanoparticle lipid interactions, and RF-heating on lipid phase behavior will be studied. In Aim 3, selective transbilayer permeability of a molecule encapsulated within the magnetoliposomes will be demonstrated via controlled-release or a novel burst-release mechanism through programmed RF heating.Intellectual Merit. The ability to selectively control phase behavior, heat, and mass transfer in soft colloidal nanoscale systems is highly desirable for the formation of next generation multifunctional therapies, nanoparticles, nanomaterials, and nanodevices. Localized RF heating in bilayers is an original concept that is expected to provide selective control over bilayer phase behavior, and in turn diffusion. This project will provide new experimental methods for the synthesis and characterization of hybrid nanoparticle/lipid assemblies. Hence, the integration of inorganic nanoparticles and biomolecular systems will be extended to include this unique class of active nanomaterials. Characterizing thermodynamic and transport properties will provide a complete picture of the assemblies, which will be needed to determine their potential as multifunctional therapeutic agents. For instance, the decorated magnetoliposomes may enhance drug delivery by providing an external trigger and yielding time and dose dependent diffusion. By inverting the problem, we also have identified a way to use the magnetoliposomes as a potential nanoscale temperature sensor.Broader Impacts. Given the minimally invasive nature and tissue penetration of RF-heating, these novel carriers would be very effective for manipulating the delivery of therapeutic agents in vivo. Opportunities are being pursued with faculty from the College of Pharmacy at URI to identify promising applications. In addition, these new structures provide suitable model systems for studying nanoparticle interactions with cellular membranes, including their role in uptake and potential toxicity. This project will also serve as an educational tool for high school, undergraduate, and graduate students. Co-PI Bose organizes a summer high school intern program and both PIs have been contacted by and will work with the New England LSAMP program to mentor students. Within our diverse laboratory groups, we intend to pair high school and undergraduate students with graduate student mentors to conduct independent projects directly related to hybrid liposomes. This activity will expand the impact of the project to beyond the traditional and expected research participation. The concepts behind this project and the results obtained will be used as teaching material in a new interdisciplinary graduate level Bionanotechnology course offered in the spring semester, and disseminated freely through a collaborative website.

多功能纳米量表疗法代表了疾病治疗的变革性新领域。脂质体提供了一个多功能和动态的平台，用于封装具有不同表面化学的功能无机纳米颗粒，以实现多种治疗目标。该项目采用了原始方法，可以选择性地装饰无机纳米颗粒的工程脂质体，并检查纳米颗粒的大小，电荷和疏水性如何影响脂质体的结构和功能。这样的复合组件将在需要在空间和暂时靶向输送的治疗应用中发挥重要作用。表面功能化的超顺磁铁氧化铁（SPIO）将用作模型纳米颗粒，因为它们已成功用作MRI对比剂，用于体内高温药物，在这种情况下，使用在无线电频率下运行的外部磁场来实现加热。对磁性体的编程RF刺激将为控制脂质体的结构和稳定性提供一种简单但可靠的方法。通过AIM 1，将形成静电和疏水组装的装饰磁性体，其结构，形态和胶体稳定性的特征。在AIM 2中，将研究选择性装饰，SPIO纳米颗粒脂质相互作用以及RF加热对脂质相行为的影响。在AIM 3中，将通过受控释放或通过编程的RF加热来证明，封装在磁质体内的分子的选择性跨贝透渗透性。在软胶体纳米级系统中选择性控制相行为，热量和传质的能力是非常需要的，对于形成下一代多功能疗法，纳米颗粒，纳米材料和纳米电视的能力。双层中的局部RF加热是一个原始概念，有望提供对双层相行为的选择性控制，进而提供扩散。该项目将为杂交纳米粒子/脂质组件的合成和表征提供新的实验方法。因此，将扩展无机纳米颗粒和生物分子系统的整合，包括这种独特的活性纳米材料。表征热力学和运输特性将提供组件的完整图片，以确定其作为多功能治疗剂的潜力。例如，装饰后的磁透明体可以通过提供外部触发器并产生时间和剂量依赖性扩散来增强药物的递送。 通过颠倒问题，我们还确定了一种使用磁质体作为潜在的纳米级温度传感器的方法。鉴于RF加热的微创性质和组织渗透，这些新型携带者对于操纵体内治疗剂的递送非常有效。 URI药学学院的教师正在寻求机会，以确定有希望的申请。此外，这些新结构还提供了用于研究纳米颗粒与细胞膜相互作用的合适模型系统，包括它们在摄取和潜在毒性中的作用。该项目还将作为高中，本科生和研究生的教育工具。 Co-Pi Bose组织了一项夏季高中实习计划，并联系了两个PI，并将与新英格兰LSAMP计划合作以指导学生。在不同的实验室小组中，我们打算将高中和本科生与研究生导师配对，以开展与混合脂质体直接相关的独立项目。这项活动将把项目的影响扩大到传统和预期的研究参与之外。该项目背后的概念和获得的结果将在春季学期提供的新的跨学科研究生Bionanotechnology课程中用作教学材料，并通过协作网站自由传播。