Nanoparticle imaging method for drug discovery and cancer therapy in humans

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.

The proposed research is aimed at the Healthy Nation prosperity outcome by providing a novel imaging method to enable the development of new drug therapies for cancer, and enable improved radiotherapy targeting to provide timely diagnosis, and hence maximise cancer therapeutic intervention by clinicians. The potential is immense as new drug therapies can cost up to 4 billion dollars to obtain FDA approval. The goal of a targeted drug delivery system is to prolong, localize, target, however roughly, 99% of the drugs administered do not reach the target site, which limit their effectiveness.

1 - Impact on Knowledge The proposal cuts across several scientific communities - engineering, physics, surface chemistry, nanoparticles, nanomedicine, ICT and clinical biochemistry - and addresses challenges that lie at the interface of these fields. The research will help transform the technologies that deliver therapies, by providing a new technology that can image the location of nanoparticles in humans. Nanoparticles have the potential to treat many conditions by acting as a scaffold or scaffolding to create new drugs, or to distort cancer cells or bacteria. It has already been demonstrated that gold nanoparticles can be used to focus radiotherapy.

2 - Impact on Society The core technology developed by the project will facilitate a transformative impact on healthcare provision, as defined by the EPSRC Healthy Nation, by optimising diagnosis and treatment and developing future therapeutic technologies. The NHS and global healthcare systems will benefit from more cost-effective personalised care, simplified patient pathways and better-informed public health intervention programmes, by the development of technology that can improve drug delivery or radiotherapy. The use of nanoparticles also has the potential to reduce the need for radiotherapy, as these can be used to apply hyperthermia to multi targets, offering treatment for cancer to different parts of the body. This technology will allow new and improved targeting of therapies to be developed that target and improve the delivery of therapeutic intervention in shorter time frames. Large-scale advance of the technology would make new cancer treatments more affordable in the developing world and will be of interest to W.H.O. for the development of new drugs for other diseases conditions.

3 - Impact on Economy The proposed research will lead to new drugs and therapies that can be personalised for the patient. Drug makers have been complaining about the difficulty of bringing new products to market in a regulatory climate that has become increasingly unpredictable and more likely to err on the side of safety, in deciding risk/benefit ratios of experimental medicines. This new technology will help reduce the risk by confirming the therapeutic payload is delivered correctly.
The development of this technology will create new jobs in the healthcare, engineering and biosciences sectors (and possibly new companies in imaging and nanotechnology) by enabling the creation of new targeted therapies for personalised medicine, ultimately leading to wealth creation by the creation of new drugs and imaging technology and reinforcing the UK's position as a leading country in healthcare technologies.

4 - Impact on People The combination of biochemistry, instrumentation, electronics design, modelling, data capture and analysis, are an attractive skill set applicable across a wide range of industries, including engineering and bio/life sciences, and our staff will be well positioned to make major contributions in these areas. The researchers in the project will gain a good appreciation of the solutions that multidisciplinary skills and engineering can provide, as well as the associated practicalities, and also gain expertise to tackle challenges within healthcare.