The researchers show that, the protein fragment, called “pHLIP” (pH (Low) Insertion Peptide) can be injected into the abdomen of a mouse, find its way into the blood and then specifically accumulate in tumors. Within 20 hours after injection of labeled pHLIP, the molecules had passed through the bloodstream and accumulated in human breast tumors grown to different “stages” on the leg of a mouse.
The researchers demonstrated that by attaching fluorescent probes to a pHLIP peptide, tumors could be detected. They expect that by attaching and delivering active agents with pHLIP, that tumors may be able to be treated. Targeting is based on the fact that most tumors, even very small ones, are acidic as a result of the way they grow.
“Since the mechanism is general, and since even very small tumors can be targeted, there is an exciting array of possible applications for pHLIP,” said Donald Engelman, Eugene Higgins Professor of Molecular Biophysics & Biochemistry at Yale and a co-author of the paper.
“Andreev and Reshetnyak [co-authors of the paper] have taken a recent discovery from our lab and we are pushing hard as a team to test possible applications,” said Engelman. “We are very excited by the possibilities for both imaging and treating tumors.”
The pHLIP molecule has three states: soluble in water, bound to the surface of a membrane, and inserted across the membrane as an alpha-helix. Under normal tissue conditions of neutral pH, the water-soluble form is favored. At acidic pH, the transmembrane alpha-helix predominates.
An earlier paper from the same groups shows that at low pH, pHLIP can move cell-impermeable molecules across a cell membrane, where they are released in the cytoplasm. “pHLIP acts as a molecular nanosyringe, inserting itself into the cell membrane and injecting compounds into cell,” said co-author Yana Reshetnyak, of the University of Rhode Island. “The transported molecules can be therapeutic or toxic to the cell, depending on the intended outcome—for treating cancer, the idea is to cause cell death.”
In addition to targeting tumors, other disease states that produce inflammation and cause tissue to be acidic are a target for pHLIP. “Acidosis is a physiological marker of many diseases — and pHLIP feels acidity,” said Reshetnyak. “Therefore, pHLIP could also be used for monitoring of disease development and therapeutic outcomes. It might play very important role in the study of arthritis, ischemia and stroke.”
Lead author Oleg Andreev said, “We believe that universal medical tests to reveal many health problems at earlier stages may be developed based on pHLIP technology”
“Our discovery is an example of the reason that the NIH and DOD support basic science—we were working on the principles of membrane protein folding, and made a discovery with important medical implications that wouldn’t have happened without the ideas and approaches used in that work,” Engelman said.
Among the applications the team is actively pursuing are PET imaging of tumors, treatment of breast cancer, and alternative designs using the principles they have already established.
Janet Rettig Emanuel | EurekAlert!
New study points the way to therapy for rare cancer that targets the young
22.11.2017 | Rockefeller University
Penn study identifies new malaria parasites in wild bonobos
21.11.2017 | University of Pennsylvania School of Medicine
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
23.11.2017 | Information Technology
23.11.2017 | Physics and Astronomy
23.11.2017 | Life Sciences