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Details of Grant 

EPSRC Reference: EP/R035008/1
Title: Stimulus-responsive nanoparticles for intraoperative NIR imaging and treatment of pancreatic cancer
Principal Investigator: Nomikou, Dr N
Other Investigators:
MacRobert, Professor AJ
Researcher Co-Investigators:
Project Partners:
Department: Surgical Biotechnology
Organisation: UCL
Scheme: Standard Research
Starts: 01 September 2018 Ends: 31 August 2021 Value (£): 316,148
EPSRC Research Topic Classifications:
Biomaterials Bionanoscience
Med.Instrument.Device& Equip.
EPSRC Industrial Sector Classifications:
Related Grants:
Panel History:
Panel DatePanel NameOutcome
25 Apr 2018 HT Investigator-led Panel Meeting - April 2018 Announced
Summary on Grant Application Form
Patients with pancreatic cancer are usually diagnosed at late stage, when the disease has progressed and is difficult to treat. Surgery is the primary treatment after diagnosis of pancreatic cancer. Surgical treatment aims to remove all or as much of the cancerous tissue as possible. However, it is difficult to identify the borders between cancerous and normal tissue and, often, fragments of the disease are left behind without being removed. This residual cancer tissue after surgical procedure will lead to further cancer progression and will reduce survival of the patient.

Current methods used to distinguish different tissue structures, such as lymph nodes, during surgery are based on fluorescence and this procedure is termed fluorescence-guided surgery or intraoperative fluorescence imaging. Indocyanine green (ICG) is an agent that can emit fluorescence when exposed to high-wavelength light, which can transmit efficiently through tissue. This agent is safe to administer through blood circulation and it has already been used in fluorescence-guided surgery. However, ICG is very unstable in the body, it loses its fluorescence within minutes after injection in the blood and most of the agent accumulates in the liver. In this project, ICG, as well as similar cyanine molecule with improved optical properties, will be incorporated inside nanosised particles and this will consequently increase blood circulation time of these agents, it will temporarily quench their fluorescence emission and it will increase their accumulation in pancreatic tumours. In addition, based on preliminary experiments, once the agent is gathered within the cancerous mass, certain molecules present in the area, such as proteolytic enzymes, will break the particles apart releasing the cyanine molecules and the fluorescence emission of the agent will be recovered only inside the tumour. This will enable surgeons to identify the borders of the cancerous tissue and improve surgical removal of the disease.

In recent work, it has been discovered that when the size of these particles is decreased under exposure to conditions similar to those in pancreatic cancer tissue, more cyanine agent can accumulate inside cancerous cells. It is also been shown that when cancer cells contain cyanine dye and are exposed to laser light, these cells are destroyed. On the basis of these findings, the nanosized particles are intended to be used, not only for fluorescence-guided surgery, but also to destroy any residual cancer tissue left behind by irradiating the surgical resection area with laser light. This intraoperative treatment will improve the outcome of surgical procedures and will improve survival of patients.

The research proposed herein includes a series of experiments for characterizing the properties of the nanosized particles that contain ICG and the improved cyanine agent. Early work will establish how these particles respond to conditions similar to those of pancreatic tumours and we will examine the efficiency of the particles in highlighting cancer tissue and in destroying the latter, using cell-based systems. A subsequent series of experiments will be conducted using experimental animals that carry pancreatic tumours. These experiments will establish the safety and the efficiency of the cyanine-containing particles in fluorescence-guided surgical removal of pancreatic tumours and in the destruction of residual cancer at the resection site. Analysis will also be performed to investigate the effect of the treatment in the biology of the cancer.

The proposed approach will improve the prognosis for patients that undergo surgery for pancreatic tumour resection and will also provide new insights for the development of combined fluorescence-guided surgery and intraoperative treatment of cancer.

Key Findings
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