Nanoparticles harvest invisible cancer biomarkers

November 22, 2011

( -- Cancer biologists have long presumed that tumor cells shed telltale markers into the blood and that finding these blood-borne biomarkers could provide an early indicator that cancer is developing somewhere in the body. While there has been some progress in finding such markers, researchers have been largely stymied in this pursuit by the fact that such proteins are present in trace amounts that are cloaked by the few proteins present in far larger amounts, such as albumin and antibodies.

Now, a research team at the George Mason University has shown that they can fish out the "invisible" proteins masked by and other high concentration proteins using porous nanoparticles decorated with a series of chemical baits, each designed to harvest specific types of trace proteins from body fluids. Better yet, hooking these proteins onto the baits, which are buried within the pores of the nanoparticles, protects them from degradation until they can be released and analyzed using .

Alessandra Luchini led the international team of investigators that designed and tested the bait-laden core-shell nanoparticles. The investigators published their work in the .

Core-shell hydrogel nanoparticles have been touted as potential that would sequester these drugs from the action of protein degrading enzymes in blood until they reach their targets in the body. Luchini and her collaborators turned this paradigm on its head, choosing to use them to instead remove proteins from the blood until they can be safely collected. The key was identifying a set of 17 molecules that the researchers could attach inside the cavity structures that exist in hydrogels. These cavities are large enough to let most proteins in, but are too small for the relatively gigantic proteins that are overwhelmingly prevalent in blood and other biological fluids. To prevent smaller fragments of albumin, which are also a major blood component, from entering the nanoparticles, the investigators added to the outer shell the chemical vinylsulfonic acid, or VSA, that actively excludes albumin fragments of all sizes.

For bait molecules, Luchini and her colleagues started with a few dye molecules that biochemists have used as protein binding agents and inhibitors of protein-protein interactions in chromatography experiments. Working from the chemical structures of these molecules, the investigators created a set of dyes that they could then react with their core-shell nanoparticles. They then mix the resulting nanoparticles with a biological fluid - whole blood, urine, and sweat, for example - and incubated for 15 minutes. The particles are collected using a centrifuge, and the captured proteins are washed out for analysis using a set of buffers.

Luchini's team showed that the nanoparticles enabled a 10,000-fold effective amplification of protein levels in the wash fluid compared to their concentration in blood. As a result, they were able to use mass spectrometry to identify a variety of proteins that were previously undetectable in blood using any type of method that would be clinically useful.

This work, which was supported in part by the National Cancer Institute, is detailed in a paper titled, "Multifunctional Core-Shell : Discovery of Previously Invisible ." Investigators from Stockholm University in Sweden, the Instituto Superiore di Sanità in Rome, Italy, and the University of Turin in Italy also participated in this study.

Explore further: Protein Cage Helps Nanoparticles Target Tumors

More information: View abstract

Related Stories

Protein Cage Helps Nanoparticles Target Tumors

January 17, 2007

Researchers at Montana State University have used an engineered form of ferritin, a cage-like iron storage protein, to both synthesize and deliver iron oxide nanoparticles to tumors. The investigators, led by Trevor Douglas, ...

Nanoscale 'Egg' Kills Tumor Cells with Platinum

January 22, 2007

Researchers at the Hong Kong University of Science and Technology have developed a nanoscale “egg” that could safely deliver platinum, a known anticancer agent, to tumor cells. Tests with this nanoscale egg, which has ...

Scientists Quantify Nanoparticle-Protein Interactions

January 13, 2010

( -- A research team at the National Institute of Standards and Technology has quantified the interaction of gold nanoparticles with important proteins found in human blood, an approach that should be useful in ...

Nanosponges harvest rare cancer marker from blood

January 19, 2011

Cancer researchers have long hypothesized that tumors release small amounts of proteins that could serve as earlier diagnostic indicators of cancer, but the search for such biomarkers has been hampered by the presence of ...

Nanoparticles working in harmony

July 15, 2011

For decades, researchers have been working to develop nanoparticles that deliver cancer drugs directly to tumors, minimizing the toxic side effects of chemotherapy. However, even with the best of these nanoparticles, only ...

Recommended for you

An engineered surface unsticks sticky water droplets

August 31, 2015

The leaves of the lotus flower, and other natural surfaces that repel water and dirt, have been the model for many types of engineered liquid-repelling surfaces. As slippery as these surfaces are, however, tiny water droplets ...

Electrical circuit made of gel can repair itself

August 25, 2015

(—Scientists have fabricated a flexible electrical circuit that, when cut into two pieces, can repair itself and fully restore its original conductivity. The circuit is made of a new gel that possesses a combination ...

Scientists grow high-quality graphene from tea tree extract

August 21, 2015

(—Graphene has been grown from materials as diverse as plastic, cockroaches, Girl Scout cookies, and dog feces, and can theoretically be grown from any carbon source. However, scientists are still looking for a ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.