Nanoparticle imaging method for drug discovery and cancer therapy in humans

用于人类药物发现和癌症治疗的纳米颗粒成像方法

• 批准号: EP/R04192X/1
• 负责人: Richard Bayford
• 金额: $ 31.53万
• 依托单位: Middlesex University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FR04192X%2F1
• 关键词: Nanoparticle; imaging; method; drug; discovery

A novel nanoparticle imaging method for drug discovery and cancer therapy in humans will be created based on the combination of gold nanoparticles (AuNPs) as contrast agent, activated with radio-frequency (RF) and imaged with electrical impedance tomography (EIT). This would use the advantage that EIT is very sensitive to impedance change due to temperature changes from the RF activation of the AuNPs. It would have the potential to replace positron emission tomography (PET) imaging with the advantage of no ionising radiation, lower cost and the high temporal resolution of EIT. This would have a wider range of applications including tracking nanoparticles used to target cancer cells and drug discovery. Key to their use is the ability to target the desired cells for therapy; at present transmission electron microscopy (TEM) or photo-thermic microscopes can be used to image them on cell lines or in some case samples removed from the patient but not in vivo. Technology like PET uses ionising radiation and MRI does not use AuNPs, as they are paramagnetic and would require many images to track the particles, which would not be cost effective. The new imaging technology could also be combined with radiotherapy to confirm the location of the AuNPs. Researchers have investigated the concept of kilovoltage radiosurgery with AuNPs for AMD (Age-related Macular Degeneration). They concluded that a prescribed dose of x-ray radiation could be delivered using almost half of the radiation when compared to a treatment without AuNPs allowing reduction of the dose delivered to the neighbouring organs such as the retinal/optic nerve by 49%.Nanoparticles have been suggested for a range of clinical applications, including as contrast agents, for drug delivery and for treatment or therapy. Nanoparticles may be delivered to the patient by injection, by ingestion or by topical application to the skin, for example. Nanoparticles are constructed to perform a function in the body, for example to reach a particular target in the body such as an organ or a tumour. Once at the target, the nanoparticles may deliver a payload or play a role in some other function such as imaging or therapy. Thus, for example, if the nanoparticle is to target a tumour, cancer biomarkers may be attached to the scaffold core. Alternatively, antibodies to specific bacteria may be attached to the NPs in order to detect sepsis.The ability to track drug delivery by attaching a nanoparticle in the human body or using AuNPs to kill cancer cells would transform cancer treatment and other conditions, for example, if cancer metastasises then AuNPs could prove a method of destroying cancer cells. Many drugs, even those discovered using the most advanced molecular biology strategies, have unacceptable side effects due to the drug interacting with healthy tissues that are not the target of the drug. The goal of a targeted drug delivery system is to prolong, localize and target however roughly 99% of the drugs administered do not reach the target site. Side effects limit our ability to design optimal medications for many diseases such as cancer, neurodegenerative diseases, and infectious diseases. Also at present technologies to track drugs use mass spectroscopy and animal experiments requiring large scale computing to provide only one image of the accumulation of the drug. The novel approach proposed in this would revolutionise this and could provide hundreds of images a second if needed. This project has considerable potential to optimise targeting.

将基于金纳米颗粒（AUNPS）作为对比剂的组合创建一种用于人类药物发现和癌症治疗的新型纳米颗粒成像方法，并用射频（RF）激活，并用电阻抗层析成像（EIT）成像。这将利用一个优势，即由于AUNP的RF激活而变化，EIT对阻抗变化非常敏感。它具有替代正电子发射断层扫描（PET）成像的潜力，而没有电离辐射，较低的成本和EIT的高时间分辨率。这将具有更广泛的应用，包括跟踪用于靶向癌细胞和药物发现的纳米颗粒。它们使用的关键是能够靶向所需细胞进行治疗的能力。目前，可以使用传输电子显微镜（TEM）或光感显微镜在细胞系上或从患者中取出的样品（而不是体内）进行对象。像PET这样的技术使用电离辐射，MRI不使用AUNP，因为它们是顺磁性的，并且需要许多图像来跟踪颗粒，这不会具有成本效益。新的成像技术也可以与放射疗法结合使用，以确认AUNP的位置。研究人员已经研究了使用AUNPS（与年龄相关的黄斑变性）AUNP的基尔诺沃特放射外科手术的概念。他们得出的结论是，与没有AUNP的治疗相比，可以使用几乎一半的X射线辐射剂量允许将剂量降低给附近的器官，例如视网膜/视神经等剂量，例如视网膜/视神经。纳米颗粒已被建议用于临床应用，包括药物递送和治疗，以进行药物递送和治疗，以进行药物治疗或治疗。纳米颗粒可以通过注射，摄入或通过局部施加到皮肤上传递给患者。构建了纳米颗粒以在体内执行功能，例如达到体内特定靶标，例如器官或肿瘤。一旦进入目标，纳米颗粒就可以提供有效载荷或在其他功能（例如成像或治疗）中发挥作用。因此，例如，如果纳米颗粒要靶向肿瘤，则可以将癌症生物标志物附加到脚手架芯上。或者，可以将特定细菌的抗体附着在NP上以检测败血症。通过在人体中附着纳米颗粒或使用AUNP杀死癌细胞来跟踪药物递送的能力，例如，如果癌症转移，则AUNP可以证明一种破坏癌症细胞的方法。许多药物，即使是使用最先进的分子生物学策略发现的药物，由于药物与不是药物靶标的健康组织相互作用，因此具有不可接受的副作用。目标药物输送系统的目的是延长，本地化和靶标，但是大约99％的药物没有到达目标部位。副作用限制了我们为许多疾病（例如癌症，神经退行性疾病和传染病）设计最佳药物的能力。目前，跟踪药物的技术也使用质谱和动物实验，需要大规模计算以提供药物积累的一张图像。提出的小说方法将彻底改变这一点，并在需要时提供数百张图像。该项目具有优化目标的巨大潜力。

项目成果

Exploiting the efficacy of Tyro3 and folate receptors to enhance the delivery of gold nanoparticles into colorectal cancer cells in vitro.

• DOI: 10.1039/d1na00318f
• 发表时间: 2021-09-14
• 期刊: Nanoscale advances
• 影响因子: 4.7

On the optimal plasmonic resonances in gold nanospheres embedded in dispersive media

关于嵌入分散介质中的金纳米球的最佳等离子体共振

• DOI: 10.23919/ursi-emts.2019.8931489
• 发表时间: 2019
• 作者: Nordebo S

Thoracic shape changes in newborns due to their position.

• DOI: 10.1038/s41598-021-83869-8
• 发表时间: 2021-02-24
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: de Gelidi S;Bardill A;Seifnaraghi N;Wu Y;Demosthenous A;Rahtu M;Kallio M;Bayford R
• 通讯作者: Bayford R

Exploiting the Efficacy of Tyro3 and Folate Receptors to Enhance the Delivery of Gold Nanoparticles into Colorectal Cancer Cells In Vitro

利用 Tyro3 和叶酸受体的功效增强金纳米颗粒体外递送至结直肠癌细胞中

• DOI: 10.21203/rs.3.rs-101290/v1
• 发表时间: 2020
• 作者: Patel N