Near-Infrared Nanopolymer Agents for Real-Time, In Vivo Imaging of Tumor Margins

用于肿瘤边缘实时体内成像的近红外纳米聚合物试剂

基本信息

批准号：
7482651
负责人：
Jianjun Wei
金额：
$ 10万
依托单位：
CFD RESEARCH CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-18 至 2009-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7482651
关键词：
Acids Address Affinity Animal Model Animals Arginine Asparagine Aspartate Back Binding Biocompatible Biodistribution Biological Models Blood Vessels Breast Carcinoma Breast-Conserving Surgery Buffers Cancer Patient Carboxylic Acids Carcinoma Cell Communication Cell Nucleolus Cell Nucleus Cell surface Cells Characteristics Chemicals Condition Depth Detection Development Devices Diagnosis Drug Delivery Systems Employee Strikes Endothelial Cells Fluorescence GFE-1 peptide Glutamine Glycine Health system High Mobility Group Proteins Human Image Imagery Imaging Techniques In Vitro Incubated Integrin Binding Integrins Invasive Ligands Light Link Lung Lymphatic Lymphatic vessel Lys-Asp Maleimides Malignant - descriptor Mammary Neoplasms Marketing Membrane Methods Military Personnel Neoplasms in Vascular Tissue Normal tissue morphology Optics Penetration Peptide Fragments Peptide Phage Display Library Peptides Permeability Pharmaceutical Preparations Pharmacologic Substance Phase Physiological Polyethylene Glycols Polymers Population Production Property Protocols documentation RGD (sequence)Range Reporting Reproducibility Research Route Screening procedure Series Side Signal Transduction Solubility Solutions Specificity Stimulus Surface System Techniques Testing Time Tissue Sample Tissues Title Toxic effect Tumor Specific Peptide United States United States Food and Drug Administration Universities Vertebral column absorption alanine aminopeptidase alanylproline arginylarginine aspartylglutamate base beryllium trifluoride biomaterial compatibility breast cancer diagnosis breast lumpectomy cancer cell cancer diagnosis cancer recurrence cellular imaging chromophore clinical application commercialization concept cost crosslink density design experience fluorophore functional group human tissue image processing improved in vivo leucylarginine lysyllysine lysylproline malignant breast neoplasm membrane dipeptidase monomer neoplastic cell noninvasive diagnosis novel optical imaging polymerization prolyl-proline prolylglutamic acid receptor receptor binding research clinical testing response success tool tumor

项目摘要

DESCRIPTION (provided by applicant): Optical imaging as a noninvasive diagnosis technique is a highly promising tool for real-time, in-vivo detection of tumor margins during breast-conserving surgery. This can decrease false-negative diagnoses and local recurrences of the cancer that occur after conventional diagnoses and lumpectomy. Its clinical application has been held back by lack of suitable imaging agents. There is a clear need to develop imaging agents for extending applications of optical imaging method for real-time breast cancer diagnosis. The challenge of a real- time agent requires deep tissue penetration and visualization, good biocompatibility and stability, as well as capability to distinguish malignant cancer cells from surrounding healthy cells. To address the challenge, we propose to develop novel near-infrared (NIR) nanopolymer agents to real-time identify tumor margins through recognition of molecules that are specifically expressed in tumor cells. A series of tumor-homing peptides for specific binding integrins on cancer cells will be introduced to the polymer agent and tested for optimizing tumor-binding specificity. Our concept is based on an intrinsic NIR-fluorescent conjugated polymer backbone which features: a) high intensity and photostability, b) deep tissue penetration, c) specific sensitivity to tumor cells, d) biocompatibility and e) low cost production. An already established conjugated polymer synthetic route, incorporating chemical and optical characterization, NIR fluorescent imaging will be the starting point for the synergistic effort. Building on our significant preliminary results, the Phase I research will first synthesize the designed agent by incorporating multi-NIR fluorophores and high-density biocompatible side-chains to the conjugated polymer backbone, while the binding peptide will be covalently linked to the side chain. Secondly, we will demonstrate the feasibility of imaging-detection of tumor cells and small clusters of tumor cells (1 mm) within a larger population of cells as proof-of-concept. Phase II efforts will focus on further development of the nanopolymer agent, and deliver mature protocols for synthesis of the NIR imaging agent. We will validate the real-time imaging of breast tumor margin of our nanopolymer agents in animal model imaging using a non-invasive optical imaging system (IVIS 50 fro Xenogen). The success of Phase II will provide a list of optical imaging agents suitable for real-time identification of breast cancer margins. The agents will be primarily marketed to pharmaceutical companies for FDA approval and clinical testing.

描述（由申请人提供）：光学成像作为一种非侵入性诊断技术是一种非常有前途的工具，用于实时，体内检测乳房疗法手术期间的肿瘤边缘。这可以减少传统诊断和肿块切除术后发生的癌症的假阴性诊断和局部复发。由于缺乏合适的成像剂，其临床应用已阻止。显然需要开发成像剂，以扩展用于实时乳腺癌诊断的光学成像方法的应用。实时药物的挑战需要深层的组织渗透和可视化，良好的生物相容性和稳定性以及能够区分恶性癌细胞与周围健康细胞的能力。为了应对挑战，我们建议通过识别在肿瘤细胞中特异性表达的分子来开发新型的近红外（NIR）纳米聚合物剂，以实时识别肿瘤边缘。一系列用于癌细胞特异性结合蛋白的肿瘤植物肽将被引入聚合物剂并进行了测试以优化肿瘤结合特异性。我们的概念基于固有的NIR荧光共轭聚合物主链，其特征是：a）高强度和光稳定性，b）深层组织渗透，c）对肿瘤细胞的特异性敏感性，d）生物相容性和e）低成本产生。 NIR荧光成像将是一种已经建立的共轭聚合物合成途径，结合了化学和光学特征，将成为协同工作的起点。在我们的重要初步结果的基础上，I期研究将首先通过将多NIR荧光团和高密度生物相容性的侧链融合到共轭聚合物主链中，而结合肽将共同链接到侧链。其次，我们将证明在较大细胞群体中，肿瘤细胞和较小的肿瘤细胞（1 mM）成像检测的可行性作为概念证明。第二阶段的努力将集中于纳米聚合物剂的进一步开发，并提供成熟的方案以合成NIR成像剂。我们将使用非侵入性光学成像系统（IVIS 50 fro trofo Xenogen）验证动物模型成像中纳米聚合物剂的乳腺肿瘤缘的实时成像。 II期的成功将提供适合实时鉴定乳腺癌边缘的光学成像剂的列表。这些代理商将主要向制药公司销售，以进行FDA批准和临床测试。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Highly water-soluble, near-infrared emissive BODIPY polymeric dye bearing RGD peptide residues for cancer imaging.

DOI：
10.1016/j.aca.2012.10.026
发表时间：
2013-01-03
期刊：
Analytica chimica acta
影响因子：
6.2
作者：
Zhu S;Zhang J;Janjanam J;Bi J;Vegesna G;Tiwari A;Luo FT;Wei J;Liu H
通讯作者：
Liu H

Highly water-soluble neutral BODIPY dyes with controllable fluorescence quantum yields.

DOI：
10.1021/ol102758z
发表时间：
2011-02-04
期刊：
ORGANIC LETTERS
影响因子：
5.2
作者：
Zhu, Shilei;Zhang, Jingtuo;Vegesna, Giri;Luo, Fen-Tair;Green, Sarah A.;Liu, Haiying
通讯作者：
Liu, Haiying