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Posted: May 30, 2006
Nanoparticles as potential biomarker harvesters
(Nanowerk Spotlight) Nanoparticles can be modified to create selective surfaces for targeted molecular interactions. As the biomarker populations present in blood are more fully characterized, nanoparticle harvesting platforms will have significant potential improve the detection of diseases at an early, more treatable stage.
A group of scientists at the Center for Applied Proteomics and Molecular Medicine at George Mason University in Virginia are conducting research to understand how nanomaterials can be engineered to have surface properties that can be used to isolate biomarkers in blood. Their recent paper, titled "Nanoparticles: potential biomarker harvesters", was published in the February 2006 edition of Current Opinion in Chemical Biology.
David Geho, first author of the paper, explained the background of their research to Nanowerk: "A large body of information is being discovered in the low abundance proteomic fraction of blood. There is widespread interest in developing high throughput tools for harnessing this information so that it can be used for early diagnosis of diseases such as cancer."
Recent application of highly sensitive mass spectrometry tools to study the proteomic content of blood has revealed a new subset of low abundance, low molecular weight (LMW) proteins that had been previously overlooked. It is in the LMW, low abundance population of blood proteins that the potential biomarker-rich population is currently thought to reside. Such biomarkers could be valuable as "fingerprints" indicating disease states or even particular stages of a disease.
One impediment to fully utilizing this information for diagnostic applications is that these molecules are found in very low abundance in blood samples.
"Recent research has demonstrated that LMW proteins and protein fragments (potential biomarkers) are noncovalently bound to high abundance resident blood proteins such as albumin" says Lance Liotta, an author of the paper. "A critical challenge for clinical proteomics is a means for separating and isolating low molecular weight biomarkers bound to carrier proteins in order to study them as candidate biomarkers using techniques such as mass spectrometry."
Nanoparticle bioconjugate harvesting platform. Nanoparticle surfaces can be engineered with functional groups that enable affinity groups such as
proteins (e.g. antibodies) to be added to their surfaces. The nanoparticle can contain an intrinsic label, such as a quantum dot, which functions as a
tracer element. The affinity molecules on the surface of the particle provide binding sites for selected proteins or protein fragments that circulate in the
blood bound to other carrier proteins, such as albumin. (Reprinted with permission from Elsevier)
The physicochemical malleability and high surface areas of nano-engineered materials make them ideal candidates for developing biomarker harvesting platforms. A simple configuration for a biomarker harvesting platform is to design a set of nanoparticles with distinct physicochemical properties.
"For example" says Geho, "the relative surface area, presence or absence of size-selective pores, and surface chemistries of nanoparticles can be tailored to provide a
physicochemically based fractionation tool for blood proteins.
"One scenario for use of these particles is to apply them to a serum sample. Following association of molecules with the particles, the particles are washed, removing the subset of unbound molecules. The molecules bound to the particles may then be eluted and analyzed" Geho explains.
There are a wide variety of substrates that could be used for such a platform, including silica particles. The approach used by Geho and his team can be extended in the future to include metal, polymeric and biomolecule-based particles as well.
"There is significant innovative potential for the development of in vitro and in vivo harvesting systems to improve the detection of diseases at an early, more treatable stage" concludes Emanuel Petricoin, also an author of the paper.