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.

基于金纳米粒子(AuNPs)作为造影剂的组合，利用射频(RF)激活和电阻抗断层扫描(EIT)成像，将创建一种新的纳米粒子成像方法，用于人类的药物发现和癌症治疗。这将利用EIT对由于射频激活AuNPs而引起的温度变化引起的阻抗变化非常敏感的优势。它有可能取代正电子发射断层成像(PET)，具有无电离辐射、成本低和EIT时间分辨率高的优点。这将有更广泛的应用，包括跟踪用于靶向癌细胞的纳米颗粒和药物发现。它们使用的关键是靶向治疗所需细胞的能力；目前，可以使用透射电子显微镜或光热显微镜在细胞线上或在某些情况下从患者身上取出但不能在体内对它们进行成像。像PET这样的技术使用电离辐射，而MRI不使用AuNPs，因为它们是顺磁性的，需要许多图像来跟踪颗粒，这将是不划算的。新的成像技术也可以与放射治疗相结合，以确定AuNPs的位置。研究人员研究了使用AuNPs进行千伏放射外科治疗AMD(老年性黄斑变性)的概念。他们的结论是，与不使用AuNPs的治疗相比，使用几乎一半的辐射可以提供规定剂量的x射线辐射，从而将向邻近器官如视网膜/视神经的剂量减少49%。纳米颗粒已被建议用于一系列临床应用，包括作为造影剂、药物输送和治疗或治疗。例如，纳米颗粒可以通过注射、摄取或局部涂抹在皮肤上传递给患者。纳米粒子的构造是为了在人体内执行某种功能，例如，到达人体内的特定靶点，如器官或肿瘤。一旦到达靶点，纳米颗粒就可以提供有效载荷，或者在成像或治疗等其他功能中发挥作用。因此，例如，如果纳米颗粒以肿瘤为靶点，则癌症生物标记物可以附着在支架核心上。或者，可以将针对特定细菌的抗体附着到NPs上，以检测败血症。通过在人体内附着纳米颗粒或使用AuNPs杀死癌细胞来跟踪药物输送的能力将改变癌症治疗和其他条件，例如，如果癌症转移，AuNPs可能被证明是一种摧毁癌细胞的方法。许多药物，甚至是那些使用最先进的分子生物学策略发现的药物，都有不可接受的副作用，因为药物与不是药物靶点的健康组织相互作用。靶向给药系统的目标是延长、本地化和靶向，但大约99%的给药药物没有到达靶点。副作用限制了我们为许多疾病设计最佳药物的能力，如癌症、神经退行性疾病和传染病。此外，目前跟踪药物的技术使用质谱学和动物实验，需要大规模的计算才能提供药物累积的一张图像。文中提出的新方法将彻底改变这一点，如果需要，每秒可以提供数百张图像。这个项目有相当大的潜力来优化目标。

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