How To Capture Quickly Cancer Markers

A nanoscale product of human cells that was once considered junk is now known to play an important role in intercellular communication and in many disease processes, including cancer metastasis. Researchers at Penn State have developed nanoprobes to rapidly isolate these rare markers, called extracellular vesicles (EVs), for potential development of precision cancer diagnoses and personalized anticancer treatments.

Lipid nanoprobes

Most cells generate and secrete extracellular vesicles,” says Siyang Zheng, associate professor of biomedical engineering and electrical engineering. “But they are difficult for us to study. They are sub-micrometer particles, so we really need an electron microscope to see them. There are many technical challenges in the isolation of nanoscale EVs that we are trying to overcome for point-of-care cancer diagnostics.”

At one time, researchers believed that EVs were little more than garbage bags that were tossed out by cells. More recently, they have come to understand that these tiny fat-enclosed sacks — lipids — contain double-stranded DNA, RNA and proteins that are responsible for communicating between cells and can carry markers for their origin cells, including tumor cells. In the case of cancer, at least one function for EVs is to prepare distant tissue for metastasis.

The team’s initial challenge was to develop a method to isolate and purify EVs in blood samples that contain multiple other components. The use of liquid biopsy, or blood testing, for cancer diagnosis is a recent development that offers benefits over traditional biopsy, which requires removing a tumor or sticking a needle into a tumor to extract cancer cells. For lung cancer or brain cancers, such invasive techniques are difficult, expensive and can be painful.

Noninvasive techniques such as liquid biopsy are preferable for not only detection and discovery, but also for monitoring treatment,” explains Chandra Belani, professor of medicine and deputy director of the Cancer Institute,Penn State College of Medicine, and clinical collaborator on the study.

We invented a system of two micro/nano materials,” adds Zheng. “One is a labeling probe with two lipid tails that spontaneously insert into the lipid surface of the extracellular vesicle. At the other end of the probe we have a biotin molecule that will be recognized by an avidin molecule we have attached to a magnetic bead.”


How to Observe Neurons In The Brain

The term a “brighter future” might be a cliché, but in the case of ultra-small probes for lighting up individual proteins, it is now most appropriate. Researchers at the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab) have discovered surprising new rules for creating ultra-bright light-emitting crystals that are less than 10 nanometers in diameter. These ultra-tiny but ultra-bright nanoprobes should be a big asset for biological imaging, especially deep-tissue optical imaging of neurons in the brain.

Working at the Molecular Foundry, a DOE national nanoscience center hosted at Berkeley Lab, a multidisciplinary team of researchers led by James Schuck and Bruce Cohen, both with Berkeley Lab’s Materials Sciences Division, used advanced single-particle characterization and theoretical modeling to study what are known as “upconverting nanoparticles” or UCNPs. Upconversion is the process by which a molecule absorbs two or more photons at a lower energy and emits them at higher energies.

Researchers at Berkeley Lab’s Molecular Foundry created upconverting nanoparticles (UCNPs) from nanocrystals of sodium yttrium fluoride (NaYF4) doped with ytterbium and erbium that can be safely used to image single proteins in a cell without disrupting the protein’s activity

The widely accepted conventional wisdom for designing bright UCNPs has been that you want to use a high concentration of sensitizer ions and a relatively small concentration of emitter ions, since too many emitters will result in self-quenching that leads to lower brightness, says Schuck, who directs the Molecular Foundry’s Imaging and Manipulation of Nanostructures Facility.

Schuck and Cohen are the corresponding authors of a paper describing this research in Nature Nanotechnology.