Anne-Mari Anton Willmore will defend her doctoral thesis „Silver nanoparticles for cancer research“ on Friday, 17. November at 14.
Professor Tambet Teesalu, PhD, University of Tartu
Gary Braun (Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California and the Center for Nanomedicine and the Department of Chemistry and Biochemistry, University of California, USA)
Associate Professor Hélder A. Santos (D.Sc. Tech.), University of Helsinki (Finland)
Description of the problem
Cancer continues to be a challenge to modern medicine. While nanotherapeutics have had some success in the past 20 years at reducing side effects and improving patient tolerance of treatment, they have not been the silver bullet that was hoped for and have not increased overall survival in patients. Clinical nanotherapeutics so far only target tumors through passive accumulation from blood circulation. Nanoparticles (NPs) targeted to tumors have yet to be approved although some are in clinical trials. It is hoped that with added targeting groups on therapeutic nanoparticles more effective treatment is possible. One way to target NPs is through the use of homing peptides, discovered by phage display, conjugated to their surface. Phage display uses massively diverse libraries of peptides that are displayed on a bacteriophage coat protein. The library can be injected systemically and then the peptide-phages that have homed to a tumor can be recovered and sequenced in order to identify homing peptides. These peptides are well suited to being synthesized and conjugated to a nanoparticle, which mimics the bacteriophage, itself a biological nanoparticle. Peptides targeting various cancers have already been discovered through phage display and some have been used successfully on nanoparticles in the pre-clinical setting. In order to validate these peptides a nanoparticle platform is necessary which is similar to the phage, but easier to use, identify microscopically, and quantify. Another useful feature of a nanoparticle platform would be to make it possible to identify intra- and extracellular particles, since most therapeutics must be delivered inside a cell in order to work.
Result and benefit
Silver nanoparticles (AgNPs) are able to provide all of the above tools. They enhance conjugated dyes, effectively scatter light for optical detection, and enable simple peptide conjugation. A biocompatible solution was developed, to dissolve the AgNPs, to make it possible to distinguish between particles taken in by cells and those that remain outside. The AgNPs were developed further to evaluate accessible target molecules on the surface of cancer cells. This would facilitate classifying different cancers to guide the selection of an appropriate treatment. Additionally, the particle composition was altered so as to enable detection and quantification of AgNPs from cells or tissues by mass spectrometry.
These particles are for expert evaluation of courier peptides, especially quantitatively.