(NANO)^2: gold nanoclusters in lipid nanodiscoidal bicelles as a potential nanodiagnostic platform: experiment and computer modeling

(NANO)^2：脂质纳米盘状 bicelles 中的金纳米簇作为潜在的纳米诊断平台：实验和计算机建模

• 批准号: 1605971
• 负责人: Mu-Ping Nieh
• 金额: $ 36.95万
• 依托单位: University of Connecticut
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-15 至 2021-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1605971&HistoricalAwards=false
• 关键词: NANO; gold; nanoclusters; lipid; nanodiscoidal

CBET - 1605971PI: Nieh, Mu-PingLipid nanocarriers containing solid nanoparticles are a promising platform for drug delivery and imaging in biomedical applications. The entrapped solid nanoparticles can be imaging contrast agents, which enhance the signal obtained in various medical imaging techniques such as magnetic resonance imaging, X-ray computerized tomography, and photoacoustic tomography. Placing the nanoparticles inside the lipid nanocarriers increases their solubility and stability, and provides a significant enhancement in luminescence due to nanoparticle aggregation. The nanoparticle-complex can also be used to enhance local heating in photothermal therapy, which uses infrared electromagnetic radiation to treat tumors and other disorders. Aggregated gold nanoparticles can enhance signals by several orders of magnitude, which is promising for high-sensitivity imaging and sensing. The goal of this project is to develop well-defined lipid nanodiscs (bicelles) that can serve as carriers for nanoparticles and investigate their performance in imaging applications. A combination of experiments and computer simulation will be used to determine the key parameters that affect arrangements of nanoparticles in bicelles and then optimize lipid composition and nanodisc formulation to achieve encapsulated clusters of nanoparticles with strong fluorescence properties. The project will provide opportunities for students at various academic levels to participate in research. Grade 5-12 STEM teachers who participate in UCONN's da Vinci Project will be introduced to research projects related to nanoparticle self-assembly. The combination of experiments and molecular dynamics simulations will provide fundamental understanding of the interactions between lipid molecules and hydrophobically-modified solid nanoparticles such as monolayer protected gold clusters and hydrophobic quantum dots. Factors that affect solid nanoparticle solubilization and clustering inside discoidal bicelles, including lipid and hydrophobic tether chain lengths, nanoparticle size, and charge density of the lipids or nanoparticle, will be examined. In addition, the relationships between local nanoparticle concentration inside the bicelles, the distance between nanoparticles, and the size of nanoparticle clusters trapped in the lipid structure and their photo-physical properties will be investigated. The joint experimental and computer modeling effort will help predict the range of desired lipid/nanoparticle composition to optimize nanoparticle encapsulation, clustering and retention. This new strategy of nanoparticle encapsulation by lipid nanocarriers will provide a fast, robust, size-controllable and environmentally friendly platform that can be easily adapted for manufacturing.

CBET-1605971PI：NiEH，Mu-PingLipid纳米载体包含固体纳米粒子，是生物医学应用中药物输送和成像的一个很有前途的平台。包裹的固体纳米颗粒可以作为成像造影剂，增强在各种医学成像技术中获得的信号，如磁共振成像、X射线计算机层析成像和光声成像。将纳米颗粒放置在脂类纳米载体中增加了它们的溶解度和稳定性，并由于纳米颗粒的聚集而显著增强了发光。这种纳米颗粒复合体还可以用于光热疗法中的局部加热，光热疗法使用红外电磁辐射来治疗肿瘤和其他疾病。聚集的金纳米颗粒可以将信号增强几个数量级，这在高灵敏度成像和传感方面具有广阔的前景。该项目的目标是开发定义明确的脂质纳米盘(双胞体)，作为纳米颗粒的载体，并研究其在成像应用中的性能。将采用实验和计算机模拟相结合的方法，确定影响纳米颗粒在二元格中排列的关键参数，然后优化脂质组成和纳米盘配方，以获得具有强荧光特性的纳米颗粒微囊团。该项目将为不同学术水平的学生提供参与研究的机会。参加康涅狄格州达芬奇项目的5-12年级STEM教师将被介绍到与纳米粒子自组装相关的研究项目中。实验和分子动力学模拟的结合将提供对脂类分子与疏水修饰的固体纳米颗粒之间相互作用的基本了解，如单分子层保护的金团簇和疏水量子点。将考察影响固体纳米颗粒在盘状双胞内的增溶和聚集的因素，包括脂类和疏水系链长、纳米颗粒的大小和脂类或纳米颗粒的电荷密度。此外，还将研究纳米粒子在双环内的局部浓度、纳米粒子之间的距离以及被困在脂质结构中的纳米粒子簇的大小与其光物理性质的关系。联合实验和计算机建模工作将有助于预测所需的脂类/纳米颗粒组成的范围，以优化纳米颗粒的包裹性、聚集性和保留性。这种通过脂质纳米载体包裹纳米颗粒的新策略将提供一个快速、坚固、尺寸可控和环境友好的平台，可以很容易地适用于制造。

项目成果

Combinational Effects of Active Targeting, Shape, and Enhanced Permeability and Retention for Cancer Theranostic Nanocarriers

• DOI: 10.1021/acsami.8b21609
• 发表时间: 2019-03-20
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Rad, Armin Tahmasbi;Chen, Ching-Wen;Nieh, Mu-Ping
• 通讯作者: Nieh, Mu-Ping

A universal discoidal nanoplatform for the intracellular delivery of PNAs

• DOI: 10.1039/c9nr03667a
• 发表时间: 2019-07-14
• 期刊: NANOSCALE
• 影响因子: 6.7
• 作者: Rad, Armin Tahmasbi;Malik, Shipra;Bahal, Raman
• 通讯作者: Bahal, Raman