Nanotechnology Applied to Clinical Biomarker Medicine: L. Liotta
Lance Liotta, Professor at George Mason University, provides Nano World News with a preview of his upcoming presentation at NSTI Nanotech 2008, and he shares with regards developments related to the technology.
George Mason University
There is a tremendous need to find novel biomarkers for sensitive and specific disease detection that will lead to a dramatic improvement in treatment outcome. Biomarkers are nucleic acids, small proteins, protein fragments, and metabolites indicative of a specific biological state that are associated with the risk of the contraction or presence of disease. Two major hurdles have prevented biomarker discovery from reaching clinical benefits: 1) biomarkers exist in exceedingly low concentrations within complex mixtures of high-abundance proteins such as albumin; 2) degradation of protein biomarkers can occur immediately following the collection of blood or body fluid as a result of endogenous or exogenous proteinases. We have introduced a charged based affinity bait molecule into N-isopropylacrylamide to produce a particle that will perform three independent functions within minutes, in one step, in solution: (a) molecular size sieving, (b) affinity capture of all solution-phase target molecules, and (c) complete protection of harvested proteins from enzymatic degradation. The captured analytes can be completely eluted from particles and are totally compatible with mass spectrometry analysis and immunoassays.
Development of Technology
This technology is being tuned to harvest and concentrate specific protein molecules out of biological fluids like blood, urine, etc. Interesting targets are known disease biomarkers like platelet derived growth factor (PDGF) or other analytes like human growth hormone (hGH) that are too rare or labile to be detected with regular clinics technology, or whose handling is currently too expensive.
Moreover, new kinds of baits are being explored, like classes of reactive dyes used in the past for affinity chromatography, in order to obtain a general affinity bait for proteins that is independent from protein charge.
The ability of hydrogel nanoparticles technology to perform a) molecular sieving, b) analytes concentration and c) protection from degradation in one step, very rapidly, and in solution is being extended to other realms beyond proteomics. Beads loaded with β-cyclodextrin are being obtained to exploit the known affinity of cyclodextrins for small metabolites to extend the use of particles to the field of metabolomics. Particles carrying boronic acid moieties are being designed and synthesized in order selectively target polysaccharides and glycopeptides in body fluids.
Dr. Liotta acknowledges the work of Dr. Alessandra Luchini, who was the author of the first publication on smart hydrohel particles: biomarker harvesting.