Nanoparticle imaging method for drug discovery and cancer therapy in humans

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将基于金纳米颗粒（AuNPs）作为造影剂的组合，通过射频（RF）激活并通过电阻抗断层扫描（EIT）成像。这将利用EIT对由aunp射频激活引起的温度变化引起的阻抗变化非常敏感的优势。它具有无电离辐射、低成本和高时间分辨率的优点，有可能取代正电子发射断层扫描（PET）成像。这将有更广泛的应用，包括跟踪用于靶向癌细胞和药物发现的纳米颗粒。使用它们的关键是能够靶向所需的细胞进行治疗；目前，透射电子显微镜（TEM）或光热显微镜可以在细胞系上或在某些情况下从患者身上取下的样本上成像，但不能在体内成像。像PET这样的技术使用电离辐射，而MRI不使用aunp，因为它们是顺磁性的，需要许多图像来跟踪粒子，这是不划算的。新的成像技术还可以与放射治疗相结合，以确定aunp的位置。研究人员已经研究了使用AuNPs进行千伏放射手术治疗AMD（年龄相关性黄斑变性）的概念。他们得出的结论是，与不使用AuNPs的治疗相比，规定剂量的x射线辐射可以使用几乎一半的辐射，从而使传递给邻近器官（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、摄入或局部应用于皮肤来传递给患者。纳米粒子的构造是为了在体内执行某种功能，例如到达体内的特定目标，如器官或肿瘤。一旦到达目标，纳米颗粒可能会提供有效载荷或在成像或治疗等其他功能中发挥作用。因此，例如，如果纳米颗粒是针对肿瘤的，癌症生物标志物可能会附着在支架核心上。或者，针对特定细菌的抗体可以附着在NPs上，以检测败血症。通过将纳米颗粒附着在人体内或使用AuNPs杀死癌细胞来追踪药物递送的能力将改变癌症治疗和其他情况，例如，如果癌症转移，那么AuNPs可能被证明是一种摧毁癌细胞的方法。许多药物，即使是那些使用最先进的分子生物学策略发现的药物，由于药物与健康组织相互作用而不是药物的目标，具有不可接受的副作用。靶向给药系统的目标是延长，定位和靶向，但大约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如癌症、神经退行性疾病和传染病设计最佳药物的能力。此外，目前追踪药物的技术使用质谱法和动物实验，需要大规模计算才能提供药物积累的一张图像。这项研究提出的新方法将彻底改变这一现状，如果需要，每秒可以提供数百张图像。该项目在优化目标方面具有相当大的潜力。

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.