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Rationally Designed Supramolecular Bio-inorganic Hydrogels for Tumour Therapy

Final Report Summary - HOT SHOT (Rationally designed supra-molecular bio-inorganic hydrogels for tumour therapy)

Directly or indirectly, cancer affects most people's lives, regardless of sex, social status or age group. Alongside cardiovascular diseases, cancer is one of the leading causes of death and imposes a huge burden of morbidity and mortality in Europe and worldwide. In addition to causing pain and suffering, cancer can substantially affect patients' ability to lead a normal life and often necessitates prolonged periods of hospitalization and informal care. These demands put significant financial and social pressure on governments, local institutions and families.

In consideration of these issues, the Medical Standing Committee of the European Science Foundation established in 2005 that cancer, together with neurodegenerative and cardiovascular diseases, are the priority targets for the development of new technologies. The project HOT SHOT wants to take part to the enormous effort that scientists are investing into cancer research. In this project, the unique physical properties of nanoscale materials are combined with current technology to develop novel and effective agents for tumour imaging and therapeutics for cancer treatment.

In HOT SHOT novel peptide-based multifunctional particles were developed. These particles are highly engineered hydrogels made of inorganic nanoparticles, polyethyleneglycol (PEG) molecules and designer peptides. These composite particles are designed to serve as drug delivery systems with controlled release, source of thermal ablation of cancer cells and contrast agents for X-ray tumour imaging. The key feature of these highly engineered particles are the coiled coil peptides that constitute the physical link of the hydrogel and whose self-assembly is controlled by environmental conditions. Both temperature and pH responsive coiled coil peptides were successfully synthesised and characterized.

Several strategies for coupling the peptides to PEG molecules to form tri-blocks were studied and attempted, including the classic peptide bond, combinatorial chemistry and click chemistry approaches. Several nanoscale materials were considered as heat sources upon near-infrared radiation, including silica/gold core/shell nanoparticles, gold nanorods and gold hollow nanospheres. International collaborations with universities in Europe and USA were established for the procurement of such materials. The organic-inorganic composite was successfully synthesised and their behaviour studied upon temperature and pH changes. A laser with near-infrared emission was built and used to trigger the disruption of the hydrogel. The hydrogel was shaped in sub-micrometer sized beads by using an electrospraying technique.

One important aim of this fellowship was to provide training in nanomaterials, peptide chemistry, as well as new instruments. On this respect, this fellowship has been a unique learning opportunity. The value of the acquired experience has been boosted by collaborations with colleagues at Imperial College London as well as scientists from renowned institutes in the UK and abroad. The characterisation of the coiled-coils behaviour led to the development of novel peptide-based pH sensor - an on-going collaboration with the London Centre for Nanotechnology - and sensor surfaces for reversible analyte binding; rationally designed peptides were also used to develop sensors with high sensitivity towards prostate specific antigen, an important biomarker for the detection of prostate cancer.

The intense research activity carried on during this fellowship has been recognised by the 2009 June Wilson Award of the London Materials Society: The experience acquired in nanomedicine for cancer research has also led to the realisation of an invited review for a major journal in the field of nanotechnology. This review aims at bridging the medical and scientific communities, encouraging collaborations and the set up of interdisciplinary research projects.