Nanotechnology for cancer diagnosis and treatment

Pancreatic cancer has the highest one-year mortality rate of any cancer with an overall five-year survival rate of just 4 %. Most pancreatic tumours are detected late at the metastatic stage and 85 % are unresectable at the time of detection. This is partially due to the limitation of current imaging systems in diagnostic accuracy.

The goal of EU-funded SAVEME (A modular nanosystems platform for advanced cancer management: nano-vehicles; tumor targeting and penetration agents; molecular imaging, degradome based therapy) consortium developed a novel nanosystems platform for diagnostic and therapeutic applications. Using a pancreatic cancer model, this platform had to integrate advanced functionalised nanoparticles and active agents according to application requirements.

In vivo localisation of this nanosystem to cancer sites requires efficient targeting. Researchers have coupled nanoparticles with tumour cell-targeting peptides and moieties designed on newly emerging cancer biomarkers such as galectin-1.

With respect to diagnostics, partners developed a wide range of 25-150 nm-sized generic polymeric nano-scale carrier particles (NCs). These were functionalised on the surface depending on their application. Biodistribution studies demonstrated that small <100 nm NCs accumulated in tumours significantly better than larger >100 nm NCs. One of the particles allowed the visualisation of the tumour in vivo by positron emission tomography with acceptable contrast up to 48 hours after administration.

The developed nanosystems for therapeutic applications target delivery of antibodies or nucleic acids as therapeutic agents. Conjugation of nanoparticles with inhibitory antibodies, anti-matrix metalloproteases (MMPs), and small interfering RNA (siRNA) molecules were designed to inhibit tumour cell growth and invasion.

A major achievement of the project was the development of NCs that can carry siRNAs into cells with high efficiency and low toxicity. These NCs effectively delivered siRNAs into human pancreatic carcinoma cells in vitro, leading to suppression of the target genes and subsequent cell death, or apoptosis. The strongest effect was achieved with delivery of siRNAs against polo-like kinase-1 (PLK-1). Another therapeutic strategy resulted in the development of antibodies targeting MMP-7 and MMP-14, which retains their function-blocking effectiveness in vitro after coupling to NCs.

The SAVEME brochure was produced to disseminate the results of the project. Researchers presented their findings in 27 scientific publications.

Research and development from the SAVEME project has enormous potential for translation into clinical practice in diagnostics and treatment of pancreatic cancer. At the same time, it will facilitate post-therapy monitoring, reducing the need for continuous biopsies.