Luminescent Oxygen Nanosensors for Tumor Hypoxia Imaging

用于肿瘤缺氧成像的发光氧纳米传感器

基本信息

  • 批准号:
    8550797
  • 负责人:
  • 金额:
    $ 31.55万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-09-25 至 2017-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Oxygenation plays a critical role in health and medicine. Deficits or excesses in cells, tissues and organisms are associated with disease, damage, poor healing, and even death. For example, hypoxia is implicated in cancer progression, metastasis, and resistance to therapies. Hypoxia inducible factor 1 (HIF-1) expression in low oxygen environments accelerates angiogenesis and promotes tumor survival, and radiation and drug treatments can be less effective when reactive oxygen is not present to enhance the tumor damage or when hypoxia-induced changes in the tumor microenvironment otherwise affect drug delivery and action. Despite the importance of oxygen partial pressure (pO2) to biomedicine, its assessment is often limited to oxygen consumption rate (OCR) measurements, invasive probes, or expensive imaging modalities. Often methods provide only average values for whole populations of cells, or are restricted to single point measurements in space or time. The long-term goal of this project is to develop a versatile material set and platform of pO2 imaging technologies that can enhance preclinical studies and aid in diagnosis, treatment and surgery in many medical contexts. Building upon success in proof of concept studies and the strengths of our team in materials synthesis, imaging, and cancer biology, the objective of this application is to develop dualemissive difluoroboron ?-diketonate-poly(lactic acid) (BF2bdkPLA) dye-polymer nanoparticles (BNPs) in conjunction with imaging methodologies for luminescence detection and ratiometric O2 sensing in breast cancer in vitro and in vivo mouse models. This objective will be accomplished by pursuing the following specific aims: 1) BNP dyes will be chemically modified for broad range emission color tuning and oxygen sensitivity modulation; imaging methods will be developed for their use in in vitro ratiometric O2 sensing (i.e. both fluorescence (F) and phosphorescence (P) detection). 2) BNP polymers will be adapted for passive and active targeting for pO2 monitoring with improved spatial specificity; targeted BNPs will be investigated in vitro and in vivo. 3) BNP hypoxia imaging agents will be tested for their ability to detect tumors, and to monitor tumor progression and radiation and chemotherapy response over time in a mouse mammary window model. The proposed cost- effective technology is innovative because it enables dynamic hypoxia imaging with improved combined spatial and temporal resolution compared to existing approaches with a modular, tunable, synthetically accessible materials platform. The expected outcome is a versatile oxygen nanosensor technology in conjunction with common optical imaging modalities to quantify pO2 in cells, tissues and in vivo. BNPs with greater specificity, tissue penetration of light, and multiplexing capability will result. This work will have a positive impact on cancer car because it will better illuminate the relationships between hypoxia, cancer progression, and treatment protocols. Ultimately, BNPs will shed light on many medical challenges by helping to map relationships between oxygenation and biological function. This is already being realized.
描述(由申请人提供):氧合在健康和医学中起着至关重要的作用。细胞、组织和有机体中的缺陷或过量与疾病、损伤、愈合不良甚至死亡有关。例如,缺氧与癌症的进展、转移和对治疗的抵抗有关。缺氧诱导因子1 (HIF-1)在低氧环境中的表达加速血管生成并促进肿瘤存活,当活性氧不存在以增强肿瘤损伤或当缺氧诱导的肿瘤微环境变化影响药物传递和作用时,放射和药物治疗可能效果较差。尽管氧分压(pO2)对生物医学具有重要意义,但其评估通常仅限于耗氧量(OCR)测量、侵入性探针或昂贵的成像方式。通常,方法只能提供整个细胞群的平均值,或者仅限于空间或时间上的单点测量。该项目的长期目标是开发一套多功能的pO2成像技术材料和平台,以加强临床前研究,并在许多医疗环境中帮助诊断、治疗和手术。基于概念验证研究的成功和我们团队在材料合成、成像和癌症生物学方面的优势,本应用程序的目标是开发双发射二氟硼?-二酮酸-聚乳酸(BF2bdkPLA)染料聚合物纳米颗粒(BNPs)与成像方法一起用于乳腺癌体外和体内小鼠模型的发光检测和比例O2传感。这一目标将通过追求以下具体目标来实现:1)BNP染料将进行化学改性,以实现宽范围发射颜色调谐和氧敏调制;将开发成像方法,用于体外比例O2传感(即荧光(F)和磷光(P)检测)。2) BNP聚合物将适应被动和主动靶向pO2监测,提高空间特异性;我们将在体外和体内研究靶向的BNPs。3)在小鼠乳腺窗口模型中,将测试BNP缺氧显像剂检测肿瘤的能力,以及监测肿瘤进展和放化疗反应的能力。与现有的模块化、可调、可综合获取的材料平台相比,该技术具有创新的成本效益,可以实现动态缺氧成像,提高了空间和时间的综合分辨率。预期的结果是一种多功能氧纳米传感器技术,结合常见的光学成像模式,定量细胞、组织和体内的pO2。BNPs具有更高的特异性,组织穿透

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

CASSANDRA L FRASER其他文献

CASSANDRA L FRASER的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('CASSANDRA L FRASER', 18)}}的其他基金

Luminescent Oxygen Nanosensors for Tumor Hypoxia Imaging
用于肿瘤缺氧成像的发光氧纳米传感器
  • 批准号:
    8716545
  • 财政年份:
    2012
  • 资助金额:
    $ 31.55万
  • 项目类别:
Luminescent Oxygen Nanosensors for Tumor Hypoxia Imaging
用于肿瘤缺氧成像的发光氧纳米传感器
  • 批准号:
    8276440
  • 财政年份:
    2012
  • 资助金额:
    $ 31.55万
  • 项目类别:
FUNCTIONALIZED RINGS VIA OLEFIN METATHESIS CATALYSIS
通过烯烃复分解催化的官能化环
  • 批准号:
    2170623
  • 财政年份:
    1994
  • 资助金额:
    $ 31.55万
  • 项目类别:
FUNCTIONALIZED RINGS VIA OLEFIN METATHESIS CATALYSIS
通过烯烃复分解催化的官能化环
  • 批准号:
    2170622
  • 财政年份:
    1994
  • 资助金额:
    $ 31.55万
  • 项目类别:

相似海外基金

More sustainable biocatalytic imine reductions to chiral amines with hydrogen-driven NADPH recycling operated in batch and continuous flow
通过批量和连续流操作的氢驱动 NADPH 回收,更可持续地生物催化亚胺还原为手性胺
  • 批准号:
    2889869
  • 财政年份:
    2023
  • 资助金额:
    $ 31.55万
  • 项目类别:
    Studentship
Organoborane-catalysed approaches to biologically active amines
有机硼烷催化制备生物活性胺的方法
  • 批准号:
    EP/Y00146X/1
  • 财政年份:
    2023
  • 资助金额:
    $ 31.55万
  • 项目类别:
    Research Grant
Transforming Amines into Complex Polycyclic Molecules and Bioactive Natural Products
将胺转化为复杂的多环分子和生物活性天然产物
  • 批准号:
    2247651
  • 财政年份:
    2023
  • 资助金额:
    $ 31.55万
  • 项目类别:
    Standard Grant
Ti-catalyzed cascading hydroaminoalkylation as a route to complex functionalized amines
Ti 催化级联氢氨基烷基化作为制备复杂官能化胺的途径
  • 批准号:
    10750347
  • 财政年份:
    2023
  • 资助金额:
    $ 31.55万
  • 项目类别:
New Photocatalytic C-C Bond-Forming Reactivity of Unprotected Primary Amines
未受保护伯胺的新光催化 C-C 键形成反应
  • 批准号:
    EP/X026566/1
  • 财政年份:
    2023
  • 资助金额:
    $ 31.55万
  • 项目类别:
    Research Grant
Nickel Cross-Coupling Cascades with α-Heteroatom Radicals to Prepare Sterically Hindered Alcohols and Amines
镍与α-杂原子自由基交叉偶联级联制备位阻醇和胺
  • 批准号:
    10604535
  • 财政年份:
    2023
  • 资助金额:
    $ 31.55万
  • 项目类别:
Mining the air for amines
开采空气中的胺
  • 批准号:
    2752688
  • 财政年份:
    2022
  • 资助金额:
    $ 31.55万
  • 项目类别:
    Studentship
Towards a better understanding of the effect of the pentafluorosulfanyl group on the lipophilicity and acid/base properties of alcohols and amines
更好地了解五氟硫基对醇和胺的亲脂性和酸/碱性质的影响
  • 批准号:
    571856-2021
  • 财政年份:
    2022
  • 资助金额:
    $ 31.55万
  • 项目类别:
    Alliance Grants
Development of Strategies for the Enantioselective Synthesis of Heterocycles and Acyclic Amines
杂环和无环胺对映选择性合成策略的发展
  • 批准号:
    10656344
  • 财政年份:
    2022
  • 资助金额:
    $ 31.55万
  • 项目类别:
Pd-Catalyzed C(sp3)-H Functionalizations Directed by Free Alcohols and Boc-Protected Amines
由游离醇和 Boc 保护的胺引导的 Pd 催化 C(sp3)-H 官能化
  • 批准号:
    10606508
  • 财政年份:
    2022
  • 资助金额:
    $ 31.55万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了