Probing Tumor Microenvironment Using Nanotechnology

利用纳米技术探测肿瘤微环境

• 批准号: 7343362
• 负责人: Rakesh K. Jain
• 金额: $ 169.29万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-07 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7343362
• 关键词: Animals; Bio-Base; Biomedical Engineering; Biosensor; Calculi; Cells; Charge; Chemicals; Cleaved cell; Clinical; Clinical Trials; Color; Data; Detection; Development; Diagnosis; Diagnostic; Diffusion; Drug Delivery Systems; Endopeptidases; Endothelium; Engineering; Ensure; Environment; Enzymes; Fluorescence; General Hospitals; Histology; Image; Immunoconjugates; In Vitro; Injection of therapeutic agent; Institutes; Joints; Label; Laser Scanning Microscopy; Malignant Neoplasms; Maps; Massachusetts; Medicine; Metabolic; Methodology; Microscopy; Molecular; Mus; Nanotechnology; Nature; Object Attachment; Operative Surgical Procedures; Oxygen; Peptide Hydrolases; Peptides; Pharmaceutical Preparations; Phenotype; Physiological; Plasma; Polyethylene Glycols; Principal Investigator; Property; Publications; Quantum Dots; Radiation therapy; Range; Research; Resources; Science; Scientist; Semiconductors; Silicates; Solid Neoplasm; Specificity; Staging; Statistical Models; Stromal Cells; Surface; System; Techniques; Technology; Testing; Therapeutic; Translational Research; Work; base; bioimaging; cancer cell; cancer therapy; chemotherapy; design; desire; improved; in vivo; innovation; insight; interstitial; intravenous injection; mathematical model; multi-photon; multidisciplinary; nanocrystal; nanoparticle; nanoscale; novel; novel strategies; particle; programs; radius bone structure; size; targeted delivery; tool; tumor; two-photon; vector

DESCRIPTION (provided by applicant): This Bioengineering Research Partnership (BRP) will exploit emerging advances in semiconductor nanocrystal-based biomedical imaging to probe the tumor microenvironment and to develop therapeutic and diagnostic strategies. To accomplish this, we have assembled a multidisciplinary team of scientists and engineers at the Massachusetts General Hospital (MGH) and Massachusetts Institute of Technology (MIT) with a successful track record of basic and translational research. Over the past decade, this team has provided unprecedented insight into the nature of transport barriers in tumors (Nature Reviews Cancer, 2002). These exciting scientific findings resulted from innovations in intravital imaging (Nature Medicine, 1997, 2001, 2003, 2004), from exploiting molecular tools and quantum dot technology (Nature Medicine, 2005), and from the development of unique in vitro, in vivo, and mathematical models (PNAS, 1998, JCO, 2006). Our discoveries to date have led to novel strategies for improving drug delivery to tumors (Science, 2005). Development Cores led by M. Bawendi (an early pioneer of quantum dots) and D. Nocera at MIT are the corner stone of this BRP. They will develop novel nanocrystal (quantum dot) constructs, biosensors, and immunoconjugates which are not only essential for all three projects in this BRP but also provide a new direction in nanocrystal based bio-imaging by creating "smart" nanocrystal probes of chemical and morphological environment. In Project 1, led by D. Fukumura and L. Munn, we aim to develop "design rules" for nanoparticles and apply these rules to make "smart" nanoparticles that, by changing their size and charge, can circumvent tumor barriers. In Project 2, led by R.K.Jain, we seek to map metabolic microenvironment of tumors with novel nanocrystal based biosensors and improve pH-sensitive chemotherapy and oxygen-sensitive radiation therapy. In Project 3, led by D. Duda and Y. Boucher, we harness the multiplexing capabilities of nanocrystal immunoconjugate probes and biosensors to develop in vivo multi-cell molecular and functional phenotyping techniques and establish a novel treatment strategy based on targeting stromal cells in tumors. A high level of scientific interaction among the three Projects, two Development Cores and four scientific Cores is a major strength of the BRP - as documented in joint publications by Project and Core leaders. Each Project will rely on multi-photon microscopy, mathematical modeling, and statistical support provided by Core A; cutting-edge molecular, cellular and histological expertise provided by Core B; superb surgical and animal support provided by Core C; and administrative support provided by Core D. We also have the resources and the clinical collaborators in place to readily take our scientific findings to clinical trials (Nature Medicine, 2004, Cancer Cell, 2007).

描述（由申请人提供）：该生物工程研究伙伴关系（BRP）将利用半导体纳米生物医学成像的新进展来探测肿瘤微环境并开发治疗和诊断策略。为了实现这一目标，我们在马萨诸塞州总医院（MGH）和马萨诸塞州理工学院（MIT）组建了一支由科学家和工程师组成的多学科团队，他们在基础研究和转化研究方面取得了成功。在过去的十年中，该团队对肿瘤中转运障碍的性质提供了前所未有的见解（Nature Reviews Cancer，2002）。这些令人兴奋的科学发现来自活体成像的创新（Nature Medicine，1997，2001，2003，2004），利用分子工具和量子点技术（Nature Medicine，2005），以及独特的体外，体内和数学模型的开发（PNAS，1998，JCO，2006）。迄今为止，我们的发现已经导致了改善肿瘤药物递送的新策略（Science，2005）。开发核心由M。Bawendi（量子点的早期先驱）和D.麻省理工学院的诺塞拉是这个BRP的基石。他们将开发新的量子点（量子点）结构，生物传感器和免疫偶联物，这些不仅是BRP中所有三个项目所必需的，而且通过创建化学和形态环境的“智能”量子点探针，为基于量子点的生物成像提供了新的方向。在项目1中，由D. Yumura和L.我们的目标是开发纳米颗粒的“设计规则”，并应用这些规则制造“智能”纳米颗粒，通过改变它们的大小和电荷，可以绕过肿瘤屏障。在由R.K.Jain领导的项目2中，我们试图用新型的基于生物传感器的生物传感器来绘制肿瘤的代谢微环境，并改善pH敏感的化疗和氧敏感的放射治疗。在项目3中，由D.杜达和Y. Boucher博士，我们利用多重免疫结合物探针和生物传感器的能力来开发体内多细胞分子和功能表型分析技术，并建立一种基于靶向肿瘤基质细胞的新型治疗策略。三个项目、两个开发核心和四个科学核心之间的高水平科学互动是BRP的主要优势-项目和核心领导人的联合出版物中有记录。每个项目都将依赖于核心A提供的多光子显微镜、数学建模和统计支持;核心B提供的尖端分子、细胞和组织学专业知识;核心C提供的一流手术和动物支持;以及核心D提供的行政支持。我们还拥有资源和临床合作者，可以随时将我们的科学发现用于临床试验（Nature Medicine，2004，Cancer Cell，2007）。