Development of Heterodyne Coherent Anti-Stokes Raman Scattering Microscopy for Monitoring Nanoparticle Drug Delivery

开发用于监测纳米颗粒药物输送的外差相干反斯托克斯拉曼散射显微镜

• 批准号: EP/G028362/1
• 负责人: Julian Moger
• 金额: $ 27.2万
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FG028362%2F1
• 关键词: Development; Heterodyne; Coherent; Anti; Stokes

At present, 95% of all potential new drug compounds cannot be directly administered as a pharmaceutical due to poor biocompatibility, i.e. they have poor solubility, unacceptable levels of toxicity, or become metabolised by the body before reaching the site of interest. Nanoparticle drug delivery can overcome these problems by encapsulating the compounds in particles less than 1 thousandth of a millimetre in size. Moreover, nanoparticles can act as depositories for controlled drug release and can be tailored to actively target specific sites within the body.Nanoparticle drug delivery is known to greatly improve the effectiveness of a pharmaceutical and has found a wide range of applications, with different routes of administration including oral, intravenous, transcutaneous and ocular. However, the mechanisms by which these nanoparticles travel through, interact with, and modify tissues and how this relates to the improved drug performance are still unclear. These are critical questions that need to be answered in order to develop future pharmaceuticals, with lower dosing rates and reduced side effects. Our ability to answers these questions is greatly hindered by that fact that there is currently no imaging modality available to directly visualise such small particles and the structure and function of the surrounding tissue, without the aid of contrast agents. Current imaging modalities derive image contrast of the nanoparticles by means of external labels. Moreover, with these techniques it not possible to detect when and how the nanoparticles release the drug without replacing the drug with an active contrast agent. We propose to test the feasibility of a novel type of optical microscopy for performing label-free measurements.Coherent Anti-Stokes Raman Scattering, or CARS, microscopy is an optical technique in which image contrast is derived from the intrinsic chemical makeup of a sample. Preliminary work has shown that CARS can be used to image nanoparticle drug carriers against a background of biological tissues. However, modifications are required to the instrument before the technique can be fully exploited. In this proposal we plan to make such modifications and test the effectiveness of the new system for monitoring nanoparticle drug delivery to tissues and cells.A successful outcome of this project will produce a tool that can provide new information of the fundamental mechanisms underlying nanoparticle drug delivery. It will allow pharmacologists to rationally design more efficient, safer, and less invasive drug delivery systems.

目前，所有潜在的新药化合物中有95%由于生物相容性差而不能作为药物直接给药，即它们具有较差的溶解性、不可接受的毒性水平或在到达目的部位之前被身体代谢。纳米颗粒药物递送可以通过将化合物封装在尺寸小于千分之一毫米的颗粒中来克服这些问题。此外，纳米颗粒还可以作为药物控释的载体，并可以被定制为主动靶向体内特定部位。纳米颗粒给药可以极大地提高药物的有效性，并且已经发现了广泛的应用，不同的给药途径包括口服、静脉内、经皮和眼部。然而，这些纳米颗粒穿过组织、与组织相互作用和修饰组织的机制，以及这与改善药物性能的关系仍不清楚。这些都是需要回答的关键问题，以便开发未来的药物，降低剂量率和减少副作用。我们回答这些问题的能力受到以下事实的极大阻碍，即目前没有成像模式可用于在没有造影剂的帮助下直接可视化这样的小颗粒以及周围组织的结构和功能。目前的成像方式通过外部标记获得纳米颗粒的图像对比度。此外，使用这些技术，不可能检测纳米颗粒何时以及如何释放药物，而不用活性造影剂代替药物。我们建议测试的可行性，一种新型的光学显微镜进行无标记measurements.Coherent反斯托克斯拉曼散射，或汽车，显微镜是一种光学技术，其中图像对比度是来自一个样品的内在化学组成。初步工作表明，汽车可用于在生物组织背景下对纳米颗粒药物载体进行成像。然而，在充分利用该技术之前，需要对仪器进行修改。本研究计划对纳米药物递送系统进行改进，并测试其在组织和细胞中的有效性。本研究的成功将为纳米药物递送的基本机制提供新的信息。它将使药理学家能够合理地设计更有效，更安全，侵入性更小的药物输送系统。

项目成果

Imaging the uptake of gold nanoshells in live cells using plasmon resonance enhanced four wave mixing microscopy.

• DOI: 10.1364/oe.19.017563
• 发表时间: 2011-08-29
• 期刊: Optics express
• 影响因子: 3.8
• 作者: Garrett N;Whiteman M;Moger J
• 通讯作者: Moger J

Effect of Microplastic on the Gills of the Shore Crab Carcinus maenas.

• DOI: 10.1021/acs.est.6b01187
• 发表时间: 2016-04
• 期刊: Environmental science & technology
• 影响因子: 11.4
• 作者: A. Watts;M. Urbina;R. Goodhead;J. Moger;C. Lewis;T. Galloway

Label-free imaging of polymeric nanomedicines using coherent anti-stokes Raman scattering microscopy

• DOI: 10.1002/jrs.3170
• 发表时间: 2012-05-01
• 期刊: JOURNAL OF RAMAN SPECTROSCOPY
• 影响因子: 2.5
• 作者: Garrett, N. L.;Lalatsa, A.;Moger, J.
• 通讯作者: Moger, J.

Imaging cortical vasculature with stimulated Raman scattering and two-photon photothermal lensing microscopy

• DOI: 10.1002/jrs.3156
• 发表时间: 2012-05-01
• 期刊: JOURNAL OF RAMAN SPECTROSCOPY
• 影响因子: 2.5
• 作者: Moger, Julian;Garrett, Natalie. L.;Uchegbu, Ijeoma
• 通讯作者: Uchegbu, Ijeoma

Ecotoxicological assessment of nanoparticle-containing acrylic copolymer dispersions in fairy shrimp and zebrafish embryos

仙女虾和斑马鱼胚胎中含纳米颗粒的丙烯酸共聚物分散体的生态毒理学评估

• DOI: 10.1039/c7en00385d
• 发表时间: 2017
• 期刊: Nano
• 影响因子: 1.2
• 作者: Galloway T