Photoactivated metallodrugs: lighting the way to novel therapies
Lead Research Organisation:
University of Manchester
Department Name: Chemistry
Abstract
It is estimated that more than one in three of us will develop cancer in our lifetime, and for one in four it will be the cause of death. Scientists play an important role in combating this illness. Worldwide activities range from basic research into understanding the causes of cancer to the subject of this proposal, which is the development of new anticancer treatments.This research is concerned with the study of new drugs that have metal atoms as important constituents (metallodrugs), and which only become toxic to cancer cells upon irradiation of light (photoactivation). The combination of light-sensitive drugs and lasers as light sources means that the site of treatment can be carefully controlled, minimising side effects and avoiding killing healthy cells. To optimise the treatment, this research will also develop new ways to irradiate cancer cells using modern lasers with optical fibre delivery, thereby allowing any part of the body to be irradiated. In addition, new ways to deliver the drugs to the cancer cells will be studied. The drug-delivery method that will be investigated is the use of liposomes, which act as microscopic spherical containers. These can be used to store large amounts of the metallodrug and to preferentially bind to cancer cells by modifying the surface of the liposome. It may even be possible to burst open and release the drugs upon demand by activating light-sensitive molecules in the liposome.Modern science invariably requires increasingly sophisticated instrumentation and technology, and cancer research is no exception. The research described in this proposal is reliant on state of the art laser systems and advanced microscopes, which are available at the specialist COSMIC centre within the University of Edinburgh. This research will also involve close collaboration with biologists and clinicians, and the longer-term view would be for these photoactivated metallodrugs and liposome delivery systems to be in clinical trials in the next 5-10 years. In this respect, this area of research is well positioned to benefit from the rapidly expanding UK biotechnology sector, thereby maximising the potential for exploitation.
People |
ORCID iD |
| Steven Magennis (Principal Investigator) |
Publications
Graham EM
(2010)
Quantitative mapping of aqueous microfluidic temperature with sub-degree resolution using fluorescence lifetime imaging microscopy.
in Lab on a chip
Kalinin S
(2010)
On the origin of broadening of single-molecule FRET efficiency distributions beyond shot noise limits.
in The journal of physical chemistry. B
Lane R
(2012)
Two-photon excitation of the fluorescent nucleobase analogues 2-AP and tC
in RSC Advances
Lane RS
(2012)
Signal enhancement in multiphoton TIRF microscopy by shaping of broadband femtosecond pulses.
in Optics express
Natrajan LS
(2010)
Two-photon luminescence from polar bis-terpyridyl-stilbene derivatives of Ir(III) and Ru(II).
in Dalton transactions (Cambridge, England : 2003)
Pudney CR
(2013)
Enzymatic single-molecule kinetic isotope effects.
in Journal of the American Chemical Society
| Description | This fellowship allowed me to start my own research group. During the fellowship, we developed several new optical tools for studying molecules, including new fluorescence-based, thermometers, 3D excitation using short pulses and measurement of DNA structure using single-molecule detection. Prior to starting this award I spent 9 months at the Heinrich Heine University in Düsseldorf working with Prof. Claus Seidel on single-molecule fluorescence spectroscopy, including fundamental studies of Förster resonance energy transfer (FRET). I then moved to Manchester in 2007 to set up my group in the Photon Science Institute (PSI). An underlying theme of my research is the study of the structure, dynamics and reactions of DNA using single-molecule methods, and the development of new tools for single-molecule experimentation. We showed that the combination of multi-parameter fluorescence detection (MFD) of single molecules in combination with molecular dynamics (MD) simulations can reveal the high-resolution global structure of branched DNA in solution, free from heterogeneity and surface effects. We also built a total internal reflection fluorescence (TIRF) microscope, allowing the study of long-term dynamics of single molecules. This was used for the multiphoton excitation of quantum dots via TIRF, with shaping of the ultrafast laser pulses. It was also used to demonstrate that enzymatic kinetic isotope effects could be measured at the single-molecule level. |
| Exploitation Route | Our work is very relevant to the growing area of single-molecule spectroscopy and several of the papers have already been highly cited. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | Prof. Anita Jones |
| Organisation | University of Edinburgh |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We performed single-molecule fluorescence measurements of branched DNA molecules. |
| Collaborator Contribution | They performed time-resolved ensemble fluorescence measurements of branched DNA molecules |
| Impact | 10.1021/ja211802z |