Design of high-performance magnetic nanovectors for combined diagnostics and therapy

Lead Research Organisation: University of Leicester
Department Name: Chemistry

Abstract

Prostate cancer is one of the major killers in British men today. There are approximately 30,000 new cases of prostate cancer per annum in the UK resulting in 10,000 reported deaths. The majority of these deaths however can be averted if prostate cancer is detected and treated early. Therefore, there is an urgent need to develop safe and efficient methods for the diagnosis and treatment of prostate tumours for which existing detection and treatments have significant shortfalls. The combination of a diagnostic and therapeutic (termed theranostic) systems provides the potential to tailor the treatment for individual patients based on the initial test results.A promising approach for the development of cancer theranostics emerging from nanotechnology is to use tiny (5-10 nm) magnetic nanoparticles (MNPs), which can act as molecular-sized probes that identify tumour cells by Magnetic Resonance Imaging (MRI), and destroy tumour tissue by heat with mild radiowave irradiation applied from outside the body (hyperthermia). However, in spite of considerable research efforts, current MNPs systems are neither sensitive enough to detect tumours in the important early-stages nor are they effective enough to produce sufficient heat to eradicate tumours using safe levels of microwave activation. A new method of MNP preparation has been pioneered at Leicester that can produce composite nanoparticles composed of a highly magnetic FeCo core and a non-toxic Au shell. We have also demonstrated the functionalisation of these MNPs can produce stable suspensions ready for the attachment of targeting molecules specific to prostate cancer. The objective of this proposal is to develop the first MNP theranostic system for prostate cancer, which will combine ultra-sensitive MR imaging with efficient and selective hyperthermia treatment. This project outlines the programme of in vitro studies required to get the technique ready for human clinical trials. To achieve this, we will prepare the FeCo@Au core shell nanoparticles with controllable size and optimize the magnetic properties. We will then link these MNPs with molecules that will target specific proteins displayed on the surface of prostate cancer cells and subsequently evaluate their MRI and hyperthermia performance. Successful implementation of this technology would provide attendant welfare benefits for patients and significant cost benefits for the UK health-care system.

Publications

10 25 50
 
Description We synthesized a serial of core-shell magnetic nanoparticles with Fe core and different shells, including Fe3O4, SiO2, Au, Cu, Ag. These group of magnetic nanoparticles possess high saturated magnetism (175 emu/g) and r2 relaxivity (494/mM.S). After surface modification, these magnetic nanoparticles can be stablized in physiological environment such as aqueous buffer and serum. Furthermore, a specific peptide targeted to Hepsin was conjugated with magnetic nanoparticle. This peptide would address the nanoparticle to prostate cancer cell surface. Currently the cell biological evaluations are under progress.
Exploitation Route collaborations with chemists, biochemists, and molecular biologists:
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description A novel multifunctionalmagnetic nanomaterial was developed for MRI diagnosis and dual-targeted drug delivery to cancer cells. This nano-system provides a promising scheme for magnetically guided tumor targeting combined with MRI diagnosis and therapy (both chemotherapy and hyperthermia)
First Year Of Impact 2012
Sector Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Policy & public services

 
Description Shenzhen Sciences & Technology Innovation grant
Amount £150,000 (GBP)
Funding ID CXZZ20120831175831692 
Organisation Shenzhen Municipal Science and Technology Innovation Council 
Sector Public
Country China
Start 01/2013 
End 09/2014
 
Description the "Hundred Talents Program" of Chinese Academy of Sciences
Amount £260,000 (GBP)
Organisation Chinese Academy of Sciences 
Sector Public
Country China
Start 01/2014 
End 12/2016
 
Title multi-functional magnetic nanoparticles 
Description We developed a novel strategy for in situ and controlled synthesis of superparamagnetic iron oxide nanoparticles (SPIONs), and demonstrated their derivative permeable magnetic nanoreactors. 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact the nanoreactors realize unique magnetic operability and zero remanence/coercivity, which greatly favors their recycling or targeting (enrichment) abilities guided by external magnetic fields, when employed as heterogeneous catalysts, or drug delivery vehicles. 
 
Description DNA binding polyamide 
Organisation University of Strathclyde
Country United Kingdom 
Sector Academic/University 
PI Contribution My research group developed a highly efficient method to prepare DNA specific binding pyrrole-imidazole polyamides. So we can provide these polyamides for the applications in biomedical and nanoelectronic areas.
Collaborator Contribution Dr. Glenn Burley and Professor Duncan Graham at University of Strathclyde applied these polyamides in DNA nanophotonics, and DNA addressed gold nanoparticle assembly.
Impact 1. Su W., Bagshaw C., Burley G*. Addressable and unidirectional energy transfer along a DNA three-way junction programmed by pyrrole-imidazole polyamides. Scientific Reports, 3, 1883, 2013. 2. Krpetic Z, Singh I, Su W, Guerrini L, Faulds K, Burley GA*, Graham D*. Directed Assembly of DNA-Functaionlized Gold Nanoparticles Using Pyrrole-Imidazole Polyamides. J Am Chem Soc, 134, 8356-8359,2012. 3. Dondi R., Su W., Griffith GA, Clark G, Burley, GA*. Highly size and shape-controlled synthesis of silver nanoparticles via a templated Tollens reaction. Small. 5, 770-776, 2012, 4. Su W., Schuster M., Bagshaw C., Rant U., Burley G*. Site-specific assembly of DNA-based photonic wire using programmable polyamides. Angew Chem int ed, 50, 2712-2715,2011. 5. Su W., Bonnard V. and Burley GA*. DNA-templated photonic arrays and assemblies: Design principles and future opportunities. Chem. Eur. J. 18, 7982-7991, 2011.
Start Year 2009
 
Title NEW PROCESS AND NEW COMPOUNDS 
Description There is provided a novel process for preparing polyamides (in particular cyclic and hairpin polyamides) comprising the step of coupling an amine with a Boc-protected amino acid monomer in the presence of diphosgene and/or triphosgene. Such a process may be performed on a solid or solution phase. 
IP Reference WO2010125382 
Protection Patent application published
Year Protection Granted 2010
Licensed No
Impact The strategy represented a significant step forward for the multiple, parallel synthesis of structurally diverse peptoids for biomedical studies and also for the large-scale production of this family of molecules for further exploration as therapeutic scaffolds.