DIAGNOSTICS
Biomarker bolsters cancer nanosensor Speedy method detects tumor-derived vesicles Arizona State University’s Ye (Tony) Hu and his colleagues have delivered what they hope will be a double dose of good news for detecting pancreatic cancer. Pancreatic cancer is one of the leading causes of cancer deaths because it often goes undetected in early stages, according to the Mayo Clinic. The researchers report a rapid and inexpensive nanoparticle-based diagnostic fueled, in part, by a biomarker on the surface of vesicles released by pancreatic tumors (Nat. Biomed. Eng. 2017, DOI: 10.1038/ s41551-016-0021). As tumors develop, they release microscopic vesicles into a person’s blood. If biosensors could isolate and identify these vesicles, researchers could potentially catch cancer early by pricking a person’s finger and analyzing blood droplets. This process would be easier and less costly than more conventional biopsies or positron emission tomography scans, Hu says. But all cells release vesicles, and determining whether those vesicles come from healthy cells or cancerous tissue is a challenge, he explains. Now he and his colleagues have found that vesicles released by pancreatic cancer tumors overexpress the surface protein ephrin type-A receptor 2, or EphA2. The researchers focused on EphA2 because of evidence collected by other cancer researchers and a computerized proteomic analysis. In this study, their diagnostic tool helps solidify the protein as a biomarker of tumor-derived vesicles. The biosensor consists of a glass slide di-
vided into wells decorated with antibodies that capture extracellular vesicles by binding to a protein biomarker on the particles. Each well also contains gold nanorods and gold nanospheres that scatter light differently and shine red and green, respectively, under a microscope. The rods are coated with antibodies specific to vesicles from pancreatic cells, and the team adorned the spheres with antibodies that bind to EphA2. Vesicles from pancreatic cancer cells thus bind both gold particle shapes. Crowding the rods and spheres onto the same vesicle causes the combo to glow yellow. The team showed that this sensor differentiates between blood from In a new sensor, a trio of antibodies helps capture healthy people, people with pancreand decorate vesicles from pancreatic cancer atic cancer, and people with pancrecells with gold nanorods (red) and nanospheres atic inflammation. The latter condi(green), causing the vesicles to glow yellow. tion is often confused with cancer in tests that use other biomarkers, Hu explains. or polymerase chain reaction,” he adds. The sensor requires minimal sample prepaPathologist Anirban Maitra agrees that ration, and its reagents are comparable in the technology is promising and innovative. cost to other immunoassay techniques, noHe works at the MD Anderson Cancer Centably enzyme-linked immunosorbent assay ter, as do some of Hu’s coworkers, although (ELISA), the team reports. The sensor also Maitra was not involved with the study. works with samples as small as 1 µL, while Maitra, however, points out that the ELISA needs more than 100 µL. study was not blinded and each group was Rajesh Sardar, who develops nanosensors small, with about 50 people. Data in smaller at Indiana University-Purdue University In- studies such as this tend to look good, he dianapolis, says the new tool is exciting and says. “Validation in larger, blinded sample transformative. “This simple, optical-based sets becomes imperative,” he says. “I am technique has the potential to screen hopeful that the PI and his team will expand patient samples much faster than ELISA their studies.”—MATT DAVENPORT
CANCER
CREDIT: NAT. BIOMED. ENG.
Engineered bacteria provide immunotherapy Some bacteria excel in environments without much oxygen. Scientists want to harness this ability and enlist the microbes to attack certain low-oxygen targets: tumors. A team of South Korean researchers reports an engineered version of a bacterium that accumulates in tumors in mice and activates immune cells to slow cancer growth (Sci. Transl. Med. 2017, DOI: 10.1126/ scitranslmed.aak9537). In the past, researchers have engineered microbes to carry anticancer payloads, such as cytotoxic proteins or molecules that
cause cancer cells to kill themselves. Now, a team led by Joon Haeng Rhee and Jung-Joon Min of Chonnam National University have developed an attenuated strain of Salmonella typhimurium that releases a protein called FlaB, which is normally part of the virulent bacteria Vibrio vulnificus. When injected into mice with transplanted tumors, the bacteria accumulated in the tumors, triggering immune cells to infiltrate the cancerous tissue. FlaB released by the bacteria then further activated the immune cells, leading to signifi-
cantly slower tumor growth compared with tumors in mice receiving injections of buffer or nonengineered S. typhimurium. Neil St. John Forbes at the University of Massachusetts, Amherst, notes that other groups have developed bacteria that release immune-activating molecules such as cytokines. But, he says, the FlaB-releasing microbes appear to have a more dramatic antitumor effect. Forbes thinks the next step is for the researchers to further investigate the mechanism behind the microbes’ success.—MICHAEL TORRICE FEBRUARY 13, 2017 | CEN.ACS.ORG | C&EN
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Science Concentrates GEOCHEMISTRY
▸ Nuked zinc isotopes hint at the moon’s formation A study of glass formed by sand that was fused during the first nuclear bomb test not only demonstrates that high temperatures fractionate zinc isotopes, but also strengthens the giant-impact theory of the moon’s formation (Sci. Adv. 2017, DOI: 10.1126/ sciadv.1602668). The moon is highly depleted in volatile elements such as zinc compared with Earth. Scientists have suggested that the volatiles likely evaporated when a planet-sized object hit the nascent Earth billions of years ago, and the moon formed from the detritus. But in lunar samples, the zinc isotope fractionation patterns—the distribution of isotope abundances relative to each other—have been difficult to interpret in the context of the giant-impact scenario. A group led by James Day of Scripps Institution of Oceanography turned to the site of the 1945 Trinity nuclear bomb test in New Mexico, which is a rare ready-made laboratory. The tremendous heat and pressures created by the nuclear blast were similar to those believed to be involved in planetary formation and can’t otherwise be simulated on Earth. The explosion melted silica on the desert floor, producing a green glass called trinitite. The researchers found that the closer the trinitite samples were to the original blast site, the more fractionated the zinc isotopes, supporting the moon-formation hypothesis.—ELIZABETH WILSON
Insulin Trehalose glycopolymer
BIOLOGICS
New polymer protects insulin Attaching a biocompatible polymer such as polyethylene glycol (PEG) to therapeutic proteins can prolong their lifetime in the bloodstream. But many of these polymers don’t stabilize protein drugs outside the body. The medicines often require refrigeration and careful handling during storage and transport, otherwise they can become inactive—with life-threatening consequences for patients. Heather D. Maynard of the University of California, Los Angeles, and colleagues have now developed a glycopolymer that, when attached to insulin, not only prolongs the protein’s lifetime in mice without toxic effects but also prevents insulin from aggregating in a test tube (Bioconjugate Chem. 2017, DOI: acs.bioconjchem.6b00659). The researchers attached a glycopolymer with side chains containing the disaccharide trehalose to insulin at two different sites. Injected into mice, the insulin-glycopolymer conjugate had about the same lifetime as an insulin-PEG conjugate, which is a combination known to increase the lifetime of insulin in the body. The insulin-glycopolymer conjugate also remained stable in a test tube when heated at 90 °C for 30 minutes and agitated with a laboratory shaker for three hours.—MELISSA PANDIKA, special to C&EN
SYNTHESIS
▸ Click chemistry reaches a new dimension In 2014, K. Barry Sharpless and coworkers at Scripps Research Institute California developed sulfur fluoride exchange (SuFEx), a simple and rapid click chemistry reac-
F F O S F F SOF4
R R NH2 Primary amine
N
R S
Aryl alcohol
F F
TBS = tert-butyldimethylsilyl
10
N
O ArOTBS
C&EN | CEN.ACS.ORG | FEBRUARY 13, 2017
O S F OAr
H R N R Alkyl amine
R
N O
R
N
S
OAr R Multidimensional tetrahedral product
dles.” One fluoride or both can then react with aryl alcohols or alkyl amines to create products that are doubly or triply substituted along the sulfur hub’s tetrahedral axes. Potential applications include the synthesis of functional polymers and small-molecule enzyme inhibitors.—STU BORMAN
TOXICOLOGY
▸ Glyphosate linked to liver troubles in rodents Glyphosate, the plant-killing molecule in the widely used herbicide Roundup, is under perpetual scrutiny for its potential toxicity in mammals. Harm could derive from the chemical’s metabolites, such as glyoxylate, that are hypothesized to react with a protein’s functionally important amino acids, including cysteine. To test that idea, Daniel K. Nomura’s group at the
CREDIT: BIOCONJUGATE CHEM.
tion that uses sulfuryl fluoride (SO2F2) to make carbon-sulfate links. They used the technique to synthesize disulfates, polysulfate polymers, and other linear products. Suhua Li, Sharpless, and coworkers have now devised a variation that kicks SuFEx click chemistry into another dimension. Using thionyl tetrafluoride (SOF4) instead of SO2F2 as a SuFEx reagent enables them to make up to three tetrahedrally oriented connections to each sulfur hub molecule instead of two linear linkages (Angew. Chem. Int. Ed. 2017, DOI: 10.1002/anie.201611048). Thionyl tetrafluoride reacts initially with a primary amino group, forming a tetrahedral iminosulfur product with two fluoride “han-
