Engineered Organic Particles of Controlled Size, Shape and Surface Chemistry for

尺寸、形状和表面化学受控的工程有机颗粒

基本信息

  • 批准号:
    8269998
  • 负责人:
  • 金额:
    $ 31.16万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-05-01 至 2014-04-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The overall goal for this project is to elucidate the mechanisms by which organic nanoparticles of controlled shape, controlled site-specific surface chemistry, tunable particle matrix composition and tunable modulus undergo endocytosis and to use these findings to engineer the intracellular release of siRNA within mammalian cells to achieve effective gene knockdown. This information, in combination with on-going efforts to understand the bio-distribution of shape controlled particles, will help to establish the rules for the rational design of nano-carriers for the effective in vivo delivery of siRNA. This will be accomplished using a unique particle synthesis method developed at the University of North Carolina called PRINT, Particle Replication in Non- wetting Templates. PRINT is an off-shoot of the emerging lithographic processes used to fabricate devices in the microelectronics industry. In aims 1 and 2, the effect of nanoparticle composition, size, shape, surface charge and ligand choice on the cellular uptake of non-targeted and targeted nanoparticles will be examined. The kinetics of cellular internalization of the nanoparticles and the effect of charge and the spatial arrangement and the density of the ligands on the particle surface will be investigated with regard to specific pathways for cellular internalization of particles. Aim 3 will explore the rational design of PRINT nanoparticles for non-targeted and targeted in vitro delivery of siRNA. As the PRINT particles enter a cell, the particulate carriers will release the siRNA based on a stimuli induced biological or chemical degradation mechanism. The effectiveness of intracellular delivery monitored by luciferase gene silencing will be evaluated as a function of particle matrix composition, particle size and shape and pathway of internalization. Aim 4 will explore rational design of PRINT nanoparticles for targeted in vivo delivery of siRNA. The PRINT nanoparticles with encapsulated anti-luciferase siRNA will be decorated with cell specific ligands (folate, transferrin) and intravenously injected into tumor bearing mice. The efficacy and efficiency of siRNA delivery to the tumor will be evaluated as a function of particle surface and matrix chemistries. Understanding the detailed interplay between particle surface chemistry and shape on effective transfection both in vitro as well as in vivo is of significant importance. PUBLIC HEALTH RELEVANCE: Small interfering RNA (siRNA) has the potential to revolutionize the treatment of a number of life threatening human diseases, particularly cancer, but one obstacle facing researchers and companies attempting to develop siRNA therapies, or any type of nucleic acid therapeutic, is efficient and specific delivery of the polyanionic molecules into the cells, tissues or organ systems of choice. Using a technique known as PRINTTM (Particle Replication in Non-wetting Templates), we are able to fabricate nanoparticles with precise control over the particle size, shape, composition, cargo and surface properties to create truly engineered drug therapies that can be used to overcome the obstacles facing researchers and to provide the tools for the rational design of nano-carriers for the effective delivery of therapeutics in vitro and in vivo.
描述(由申请人提供):该项目的总体目标是阐明受控形状、受控位点特异性表面化学、可调颗粒基质组成和可调模量的有机纳米颗粒进行内吞作用的机制,并使用这些发现来设计哺乳动物细胞内siRNA的细胞内释放,以实现有效的基因敲减。这些信息与正在进行的了解形状控制颗粒生物分布的努力相结合,将有助于建立合理设计纳米载体的规则,以有效地在体内递送SiRNA。这将使用北卡罗来纳州大学开发的独特的颗粒合成方法来完成,该方法称为PRINT,非润湿模板中的颗粒复制。PRINT是用于制造微电子工业中的器件的新兴光刻工艺的分支。在目标1和2中,将检查纳米颗粒组成、尺寸、形状、表面电荷和配体选择对非靶向和靶向纳米颗粒的细胞摄取的影响。细胞内化的纳米颗粒的动力学和电荷的影响和空间排列和粒子表面上的配体的密度将被调查关于颗粒的细胞内化的特定途径。目的3探索PRINT纳米粒的合理设计,用于siRNA的非靶向和靶向体外递送。当PRINT颗粒进入细胞时,颗粒载体将基于刺激诱导的生物或化学降解机制释放siRNA。通过荧光素酶基因沉默监测的细胞内递送的有效性将作为颗粒基质组成、颗粒大小和形状以及内化途径的函数进行评价。目的4探索PRINT纳米粒的合理设计,用于siRNA的体内靶向递送。具有包封的抗荧光素酶siRNA的PRINT纳米颗粒将用细胞特异性配体(叶酸、转铁蛋白)修饰,并静脉内注射到荷瘤小鼠中。siRNA递送至肿瘤的功效和效率将作为颗粒表面和基质化学的函数进行评估。了解颗粒表面化学和形状之间的详细相互作用对体外和体内有效转染具有重要意义。 公共卫生相关性:小干扰RNA(siRNA)具有彻底改变许多威胁生命的人类疾病(特别是癌症)的治疗的潜力,但是试图开发siRNA疗法或任何类型的核酸疗法的研究人员和公司面临的一个障碍是将聚阴离子分子有效且特异性地递送到所选择的细胞、组织或器官系统中。使用称为PRINTTM(非润湿模板中的颗粒复制)的技术,我们能够制造对颗粒大小,形状,组成,货物和表面性质进行精确控制的纳米颗粒,以创建真正的工程药物疗法,可用于克服研究人员面临的障碍,并为合理设计纳米载体提供工具,用于体外和体内有效递送治疗药物。

项目成果

期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Tunable bifunctional silyl ether cross-linkers for the design of acid-sensitive biomaterials.
  • DOI:
    10.1021/ja108568g
  • 发表时间:
    2010-12-22
  • 期刊:
  • 影响因子:
    15
  • 作者:
    Parrott, Matthew C.;Luft, J. Chris;Byrne, James D.;Fain, John H.;Napier, Mary E.;DeSimone, Joseph
  • 通讯作者:
    DeSimone, Joseph
Rendering protein-based particles transiently insoluble for therapeutic applications.
使基于蛋白质的颗粒暂时不溶以用于治疗应用。
  • DOI:
    10.1021/ja302363r
  • 发表时间:
    2012-05-30
  • 期刊:
  • 影响因子:
    15
  • 作者:
    Xu, Jing;Wang, Jin J.;Luft, J. Christopher;Tian, Shaomin;Owens, Gary, Jr.;Pandya, Ashish A.;Bergund, Peter;Pohlhaus, Patrick;Maynor, Benjamin W.;Smith, Jonathan;Hubby, Bolyn;Napier, Mary E.;DeSimone, Joseph M.
  • 通讯作者:
    DeSimone, Joseph M.
Engineering nanomedicines using stimuli-responsive biomaterials.
  • DOI:
    10.1016/j.addr.2012.01.003
  • 发表时间:
    2012-08
  • 期刊:
  • 影响因子:
    16.1
  • 作者:
    Wang, Yapei;Byrne, James D.;Napier, Mary E.;DeSimone, Joseph M.
  • 通讯作者:
    DeSimone, Joseph M.
Future of the particle replication in nonwetting templates (PRINT) technology.
  • DOI:
    10.1002/anie.201209145
  • 发表时间:
    2013-06-24
  • 期刊:
  • 影响因子:
    16.6
  • 作者:
    Xu, Jing;Wong, Dominica H. C.;Byrne, James D.;Chen, Kai;Bowerman, Charles;DeSimone, Joseph M.
  • 通讯作者:
    DeSimone, Joseph M.
Incorporation and controlled release of silyl ether prodrugs from PRINT nanoparticles.
从印刷纳米颗粒中掺入和受控释放甲硅烷基醚前药。
  • DOI:
    10.1021/ja301710z
  • 发表时间:
    2012-05-09
  • 期刊:
  • 影响因子:
    15
  • 作者:
    Parrott, Matthew C.;Finniss, Mathew;Luft, J. Chris;Pandya, Ashish;Gullapalli, Anuradha;Napier, Mary E.;Desimone, Joseph M.
  • 通讯作者:
    Desimone, Joseph M.
{{ 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 }}

JOSEPH M. DESIMONE其他文献

JOSEPH M. DESIMONE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('JOSEPH M. DESIMONE', 18)}}的其他基金

PRINT: Nanoparticles: "Calibration Quality" Nano-tools for Studying the Effect of
打印:纳米颗粒:用于研究效果的“校准质量”纳米工具
  • 批准号:
    8540371
  • 财政年份:
    2013
  • 资助金额:
    $ 31.16万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    8540392
  • 财政年份:
    2013
  • 资助金额:
    $ 31.16万
  • 项目类别:
Education/Training and Outreach Activities
教育/培训和外展活动
  • 批准号:
    8540394
  • 财政年份:
    2013
  • 资助金额:
    $ 31.16万
  • 项目类别:
Developmental Projects and Trans-Alliance Activities
发展项目和跨联盟活动
  • 批准号:
    8540395
  • 财政年份:
    2013
  • 资助金额:
    $ 31.16万
  • 项目类别:
Carolina Center of Cancer Nanotechnology Excellence
卡罗莱纳州癌症纳米技术卓越中心
  • 批准号:
    7963527
  • 财政年份:
    2010
  • 资助金额:
    $ 31.16万
  • 项目类别:
Carolina Center of Cancer Nanotechnology Excellence
卡罗莱纳州癌症纳米技术卓越中心
  • 批准号:
    8309355
  • 财政年份:
    2010
  • 资助金额:
    $ 31.16万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    7982960
  • 财政年份:
    2010
  • 资助金额:
    $ 31.16万
  • 项目类别:
Carolina Center of Cancer Nanotechnology Excellence
卡罗莱纳州癌症纳米技术卓越中心
  • 批准号:
    8136711
  • 财政年份:
    2010
  • 资助金额:
    $ 31.16万
  • 项目类别:
Developmental Projects and Trans-Alliance Activities
发展项目和跨联盟活动
  • 批准号:
    7982962
  • 财政年份:
    2010
  • 资助金额:
    $ 31.16万
  • 项目类别:
PRINT: Nanoparticles: "Calibration Quality" Nano-tools for Studying the Effect of
打印:纳米颗粒:用于研究效果的“校准质量”纳米工具
  • 批准号:
    7982949
  • 财政年份:
    2010
  • 资助金额:
    $ 31.16万
  • 项目类别:

相似海外基金

Unraveling Adverse Effects of Checkpoint Inhibitors Using iPSC-derived Cardiac Organoids
使用 iPSC 衍生的心脏类器官揭示检查点抑制剂的副作用
  • 批准号:
    10591918
  • 财政年份:
    2023
  • 资助金额:
    $ 31.16万
  • 项目类别:
Optimization of mRNA-LNP vaccine for attenuating adverse effects and analysis of mechanism behind adverse effects
mRNA-LNP疫苗减轻不良反应的优化及不良反应机制分析
  • 批准号:
    23K15383
  • 财政年份:
    2023
  • 资助金额:
    $ 31.16万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Elucidation of adverse effects of combined exposure to low-dose chemicals in the living environment on allergic diseases and attempts to reduce allergy
阐明生活环境中低剂量化学品联合暴露对过敏性疾病的不良影响并尝试减少过敏
  • 批准号:
    23H03556
  • 财政年份:
    2023
  • 资助金额:
    $ 31.16万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Green tea-based nano-enhancer as an adjuvant for amplified efficacy and reduced adverse effects in anti-angiogenic drug treatments
基于绿茶的纳米增强剂作为抗血管生成药物治疗中增强疗效并减少不良反应的佐剂
  • 批准号:
    23K17212
  • 财政年份:
    2023
  • 资助金额:
    $ 31.16万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Effects of Tobacco Heating System on the male reproductive function and towards to the reduce of the adverse effects.
烟草加热系统对男性生殖功能的影响以及减少不利影响。
  • 批准号:
    22H03519
  • 财政年份:
    2022
  • 资助金额:
    $ 31.16万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Mitigating the Adverse Effects of Ultrafines in Pressure Filtration of Oil Sands Tailings
减轻油砂尾矿压力过滤中超细粉的不利影响
  • 批准号:
    563657-2021
  • 财政年份:
    2022
  • 资助金额:
    $ 31.16万
  • 项目类别:
    Alliance Grants
1/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
1/4-破译ECT结果和不良反应的机制(DECODE)
  • 批准号:
    10521849
  • 财政年份:
    2022
  • 资助金额:
    $ 31.16万
  • 项目类别:
4/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
4/4-破译ECT结果和不良反应的机制(DECODE)
  • 批准号:
    10671022
  • 财政年份:
    2022
  • 资助金额:
    $ 31.16万
  • 项目类别:
2/4 Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
2/4 ECT 结果和不良反应的破译机制(DECODE)
  • 批准号:
    10670918
  • 财政年份:
    2022
  • 资助金额:
    $ 31.16万
  • 项目类别:
Downsides of downhill: The adverse effects of head vibration associated with downhill mountain biking on visuomotor and cognitive function
速降的缺点:与速降山地自行车相关的头部振动对视觉运动和认知功能的不利影响
  • 批准号:
    2706416
  • 财政年份:
    2022
  • 资助金额:
    $ 31.16万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了