Next-Generation Quantum Dots for Molecular and Cellular Imaging of Cancer

用于癌症分子和细胞成像的下一代量子点

基本信息

批准号：
8547022
负责人：
Andrew Michael Smith
金额：
$ 22.91万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-03 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8547022
关键词：
Active Biological Transport Adsorption Alloys Antibodies Artificial nanoparticles Award Behavior Binding Biological Biotin Blood Blood Circulation Cancer Biology Caveolae Cells Chemicals Chemistry Color Complex Crowding Data Development Diffusion Drug Delivery Systems Drug Formulations Electronics Engineering Ensure Environment Exhibits Fluorescence Fluorescent Dyes Fluorescent Probes Generations Goals Histidine Human Image Interdisciplinary Study Lead Length Ligands Malignant Neoplasms Mechanics Mediating Medicine Mentors Metals Microscopic Microscopy Modeling Nanotechnology Neoplasms in Vascular Tissue Optics Penetration Peptides Pharmaceutical Preparations Pharmacotherapy Phase Postdoctoral Fellow Process Property Proteins Pump Quantum Dots Recombinant Proteins Research Research Institute Research Personnel Research Project Grants Research Proposals Resistance Semiconductors Series Serum Proteins Site Solid Neoplasm Streptavidin Surface Surface Properties System Techniques Technology Therapeutic Time Tissues Training Transport Process Treatment Efficacy Universities Work aerobic respiration control protein base cancer imaging clinical application clinically significant design improved in vivo interstitial intravital microscopy macromolecule malignant breast neoplasm molecular/cellular imaging nanocrystal nanoparticle next generation novel particle protein aminoacid sequence quantum research study self assembly single molecule surface coating targeted delivery transcytosis tumor tumor microenvironment uptake

项目摘要

Project Summary The aim of this research proposal is to develop a new class of fluorescent nanoparticles for highly sensitive and multicolor imaging of the tumor microenvironment in vivo toward understanding and improving nanoparticle drug delivery. We will focus on semiconductor quantum dots (QDs), which are nanocrystals that exhibit bright fluorescence and unique optical and electronic properties. We have recently designed a new class of quantum dots called 'alloyed quantum wells,' which have equalized fluorescence brightness across a broad spectrum of colors. This novel property is not available from organic dyes, fluorescent proteins, or conventional quantum dots, and will enable quantitative studies of nanoparticle drug delivery to solid tumors. The basic idea is that we can modify the size, surface chemistry, or targeting ligands on these multicolor probes to model nanoparticle drug formulations, which can then be quantitatively compared for uptake and penetration in solid tumors. Because these particles are immensely bright on the single molecule level, intravital microscopy of solid tumors will allow a single-molecule, mechanistic understanding of the rate-limiting steps of drug delivery in a multicolor fashion. This simultaneous multicolor approach is critical for comparisons in the heterogeneous tumor microenvironment, and is not possible with conventional optical probes. In this proposal, we will optically engineer these nanoparticles, develop inert surface coatings for compact sizes and long circulation times in blood, and develop new high-precision bioconjugation strategies based on self- assembly principles. We will use these new probes to image the microscopic processes of targeted-delivery to tumors, concentrating on caveolae-mediated transcytosis, an active transport process that has recently been shown to efficiently pump nanoparticles from the tumor blood vessels into the interstitial tissue. These studies will implement highly relevant orthotopic models of human breast cancer that will ensure clinical significance of the findings. During the mentored phase of this award, the candidate will be co-mentored by Dr. Shuming Nie of Emory University and Dr. Jan Schnitzer of the Proteogenomic Research Institute for Systems Medicine, and will be trained in the use of orthotopic models of human cancer, intravital microscopy techniques, and antibody- based tumor targeting strategies. Both of these mentors are leaders in their respective fields of nanotechnology and cancer biology, which will enable a convergence of expertise to guide this interdisciplinary research project and to facility the transition of the candidate from a mentored postdoctoral fellow to an independent investigator in an academic setting.

项目概要该研究计划的目的是开发一种新型荧光纳米粒子，用于高灵敏度体内肿瘤微环境的多色成像，以了解和改善纳米颗粒药物输送。我们将重点关注半导体量子点（QD），这是一种纳米晶体，表现出明亮的荧光和独特的光学和电子特性。我们最近设计了一个新的一类被称为“合金量子阱”的量子点，它在整个量子点上具有均衡的荧光亮度广谱的颜色。这种新颖的特性是有机染料、荧光蛋白或有机染料所不具备的。传统的量子点，将使纳米颗粒药物输送到实体瘤的定量研究成为可能。基本思想是我们可以修改这些多色的尺寸、表面化学或靶向配体探针来模拟纳米颗粒药物配方，然后可以定量比较其吸收和实体瘤中的渗透。因为这些粒子在单分子水平上非常明亮，实体瘤的活体显微镜检查将允许对限速的单分子机制了解以多色方式输送药物的步骤。这种同步多色方法对于比较至关重要在异质肿瘤微环境中，这是传统光学探针不可能实现的。在这个根据提案，我们将对这些纳米颗粒进行光学设计，开发尺寸紧凑的惰性表面涂层，血液循环时间长，并开发基于自我的新型高精度生物共轭策略装配原则。我们将使用这些新探针对靶向递送的微观过程进行成像肿瘤，集中于小凹介导的转胞吞作用，这是一种最近被研究的主动转运过程显示可以有效地将纳米粒子从肿瘤血管泵入间质组织。这些研究将实施高度相关的人类乳腺癌原位模型，这将确保临床意义调查结果。在该奖项的指导阶段，候选人将由聂树明博士共同指导埃默里大学的教授和系统医学蛋白质基因组研究所的 Jan Schnitzer 博士，以及将接受使用人类癌症原位模型、活体显微镜技术和抗体的培训基于肿瘤靶向策略。这两位导师都是各自领域的领军人物纳米技术和癌症生物学，这将使专业知识的融合来指导这一跨学科研究项目并促进候选人从受指导的博士后研究员过渡到学术环境中的独立调查员。